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
The Office acknowledges the receipt of Applicant’s restriction election filed on
March 16, 2026 Applicant elects Group I, claims 1, 3, 5, 8, 13-14, 18 and 56 without traverse.
The restriction is made final.
Claim Status
2. Claims 1, 3, 5, 8, 13-14, 18, 20-26, 30-35, 37-47, 49-51 and 53-56, are pending. Claims 2, 4, 6-7, 9-12, 15-17, 19, 27-29, 36, 48 and 52, are canceled. Claim 20-26, 30-35, 37-47, 49-51 and 53-55, is withdrawn. Claims 1, 3, 5, 8, 13-14, 18 and 56, are examined in the instant application.
Priority
3. This application is claiming the benefit of Provisional Application No. 63/310,518 filed February 15, 2022.
Information Disclosure Statement (IDS)
4. The IDS submitted on August 12, 2024 has been considered. Signed copy is attached.
Claim objection
Claims 1, 3, 5, 8, 13-14, 18 and 56, are objected to because of the following informalities:
Claims 1, 3, 5, 8, 13-14, 18 and 56, the term “eucalyptus” needs to italicized.
Claim 18, the recitation “nucleic acid sequence” is mentioned twice.
Appropriate correction is required.
Specification
The disclosure is objected to because of the following:
The abstract of the disclosure is objected to because the Abstract needs to be on a separate sheet. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Pg. 68, line 29 on the specification dated 12/08/2024.
Claim Rejections - 35 USC § 112(b)
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 56 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 56 recites the limitation “any of the foregoing” rendering the metes and bounds of the claim indefinite because it is not clear what is meant by the limitation as the claim requires one of the nucleotide sequences to characterize the plant.
Claim Rejections - 35 USC § 112(a)(Written Description)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 3, 5, 8, 13-14, 18 and 56, 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.
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 producing transgenic eucalyptus plant comprising a nucleic acid construct comprising, Cry2Aa (SEQ ID NO: 1 amino acid and SEQ ID NO: 2 nucleic acid), Cry1Ab (SEQ ID NO: 3 amino acid and SEQ ID NO: 4 nucleic acid), and Cry1Bb (SEQ ID NO: 5 amino acid and SEQ ID NO: 6 nucleic acid) resulting in pesticidal activity against Thyrinteina arnobia and Physocleora dukinfeldia (see Example 6 and pg. 36 table 7).
Claims encompass any nucleic acid sequence encoding Cry2A, Cry1Ab and Cry1Bb or an active portion thereof having synergistic pesticidal activity to any living organism.
Claims 1, 3, 5, 8, 13-14, 18 and 56, are directed to a transgenic plant expressing a nucleic acid construct comprising a Cry2A, Cry1Ab and Cry1Bb or an active portion thereof resulting in pest resistance to any pest.
(1) Applicant has not described structures within the nucleic acid and amino acid sequence of SEQ ID NOs: 1-6, respectively, which is an active portion thereof, that confer functionality; (2) Applicant has not described a representative number of species from the genus of structures having at least 95% sequence identity to SEQ ID NOs: 1-6 or active portion thereof, respectively (e.g., see sequence search results); (3) Applicant has not adequately described the structures of Cry2A, Cry1Ab and Cry1Bb that would result in functional activity; and (4) The specification describes that TG event No. 49 had a particular insertion point that conferred resistance in eucalyptus however the Applicant has not described all possible insertion points that would result in conferring synergistic resistance.
Claim 1 is directed to a transgenic plant expressing Cry2A, Cry1Ab and Cry1Bb or active portion thereof. The claims encompass Cry2A, Cry1Ab and Cry1Bb or active portion thereof from Bacillus thuringiensis having any nucleic acid structure or portions of the protein. Applicant does not recite any other structures besides SEQ ID NOs: 1-6 or describe a representative number of sequences from the broad genus of Cry2A, Cry1Ab and Cry1Bb or active portion thereof having functional activity.
Moreover, Cry2A, Cry1Ab and Cry1Bb proteins are have a broad range of pesticidal activity, however they do not target all types of pest such as certain insects or rodents. For example, Guimarães et al. “Short-term evaluation in growing rats of diet containing Bacillus thuringiensis Cry1Ia12 entomotoxin: nutritional responses and some safety aspects” 2010, Journal of biomedicine & biotechnology vol. : 630267 (U) describes that ribosomal proteins “express insecticidal genes (Cry genes) from Bacillus thuringiensis (Bt) stand out among the most commercialised. However, these genes confer resistance to major lepidopteran insect-pests [3] but are inefficient regarding the cotton boll weevil” … “[n]umerous data from toxicity studies have not shown any significant adverse effects of Cry proteins on mammals“ (pgs.1-2). Guimarães et al. describes that Cry proteins do not target all pest even in the lepidopteran insect-pests genus.
The specification has not described the conserved regions, motifs, features, or structures that are needed in order to confer Cry2A, Cry1Ab and Cry1Bb function or the synergistic effect of claim 14 in the active portions thereof. As such, and based on the state of the art, the nucleic and amino acid sequences and active portions thereof as encompassed by the claims may not yield plants with the trait as claimed or having synergistic activity.
The issue with active portions thereof is that the specification does not adequately describe the size, region, location, motifs, or domains that would produce synergistic pesticidal activity. Therefore, one skilled in the art would not be able to predictably produce a transgenic eucalyptus plant comprising a nucleic acid construct with only active portions that would result in broad resistance to insect pest infestation or having synergistic pesticidal activity.
Moreover, the specification has not provided a representative number of species from the broad genus of sequences having at least 95% sequence identity to SEQ ID NO: 1-6 or active portions thereof retaining cry protein functional activity. Therefore, one skilled in the art would appreciate that Applicant does not possess the genus of structures as claimed and which retain functionality, especially active portions thereof.
Furthermore, claims 3, and 5 encompass a protein sequence having at least 95% identity to SEQ ID NO: 1, 3 and 5, or the amino acid sequence having at least 95% identity to SEQ ID NO: 2, 4 and 6. This requires the specification to describe the nucleic acid sequences encoding such proteins.
However, the specification does not describe a coding sequence having at least 95% identity to SEQ ID NO: 1, 3 and 5, or a polypeptide with at least 95% identity to SEQ ID NO: 2, 4 and 6, which leads to synergistic pesticidal activity.
A nucleic acid sequence having at least 95% identity to SEQ ID NOs: 2, 4 and 6 would have 95, 93 and 98 nucleic acid substitutions relative to SEQ ID NOs: 2, 4 and 6, respectively, while a polypeptide with at least 95% identity to SEQ ID NOs: 1, 3 and 5 would have 32, 31 and 33 amino acid substitutions relative to SEQ ID NOs: 1, 3 and 5, respectively.
These polynucleotide and polypeptides would encompass 395, 393 and 398 and 1932, 1931 and 1933 distinct gene and protein variants, respectively. In the absence of describing where in the sequence of SEQ ID NOs: 2, 4 and 6 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: 1, 3 and 5, and lead to the function of synergistic pest resistance.
The specification fails to provide an adequate description of the motifs, catalytic domains, etc. in these sequences that confers functional activity. Applicant has described one structure/sequence which is not a representative number of structures/sequences from the genus of sequences having 95% sequence identity to SEQ ID NO: 1-6, or active portions thereof that retain Cry2A, Cry1Ab and Cry1Bb protein function and in turn confer synergistic pest resistance.
This rationale and rejection also applies to the genus of sequences as encompassed by instant claim 8: the specification fails to describe a representative number of sequences that retain functional activity, fails to describe the domains or motifs needed for functional activity, and fails to provide working examples. All of this is critical because the art fails to describe a sequence with at least 90% sequence identity to SEQ ID NO: 36 that has rubisco promoter functional activity.
Additionally, the specification does not describe that all constructs expressing SEQ ID NOs:1-6 will confer synergistic pesticidal activity when transgenically integrated into the eucalyptus plant. The specification describes synergistic pesticidal activity occurred only when certain conditions were met.
Specifically, the specification describes that a particular insertion point found in transgenic event No. 49 where the insertion of the construct occurred in Eucalyptus urophylla hybrid chromosome 3 short allele 420 base pairs upstream of the gene Eucgr.C03308.1 (pg. 36 table 7 and pg. 69 lines 19-30).
Here, the claim encompasses simultaneously expressing all three Cry proteins to achieve synergistic pesticidal activity. However, the specification specifically describes only one insertion point to achieve a synergistic effect. Therefore, the specification has not adequately described a representative number of transgenic plants as claimed wherein the plant has increased resistance to any possible pest or wherein a synergistic effect is obtained.
Because of the lack of a description of a representative number of structures/sequences and plants with synergistic pesticidal activity, 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 synergistic pesticidal resistance.
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
Claim Rejections - 35 USC § 112(a)(Enablement)
Claims 1, 3, 5, 8, 13-14, 18 and 56, 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 producing transgenic eucalyptus plant comprising a nucleic acid construct comprising, Cry2Aa (SEQ ID NO: 1), Cry1Ab (SEQ ID NO: 3), and Cry1Bb (SEQ ID NO: 5) resulting in pesticidal activity against Thyrinteina arnobia and Physocleora dukinfeldia, does not reasonably provide enablement for a plant expressing a nucleic acid construct comprising any structure of Cry2Aa, Cry1Ab and Cry1Bb or active portion thereof or wherein said sequences have as little as 95% sequence identity to SEQ ID NOs:1-6. 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, 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. 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 transgenic eucalyptus plant comprising any Cry2Aa, Cry1Ab and Cry1Bb or active portion thereof having as little as 95% sequence identity to SEQ ID NOs:1-6 resulting in increased resistance to any insect or a synergistic effect on increasing resistance to insect pest infestation.
(B) The nature of the invention.
The nature of the invention is transgenic eucalyptus plant comprising a nucleic acid construct comprising, Cry2Aa (SEQ ID NOs: 1 amino acid and 2 nucleic acid), Cry1Ab (SEQ ID NOs: 3 amino acid and 4 nucleic acid), and Cry1Bb (SEQ ID NOs: 5 amino acid and 6 nucleic acid) (example 6) resulting in pesticidal activity against Thyrinteina arnobia and Physocleora dukinfeldia (pg. 36 table 7).
(C) The state of the prior art
The state of the prior art does not teach a nucleic acid construct comprising eucalyptus plants comprising any Cry2Aa, Cry1Ab and Cry1Bb or active portion thereof having as little as 95% sequence identity to SEQ ID NOs:1-6 resulting in synergistic pesticidal activity in all living organisms at any insertion point.
(D) The level of one of ordinary skill
The level of one of ordinary skill in the art is high.
(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.
Claims are directed to a transgenic plant expressing a nucleic acid construct comprising a Cry2A, Cry1Ab and Cry1Bb or an active portion thereof resulting in pest resistance to any pest.
(1) Applicant has not taught structures within the nucleic acid and amino acid sequence of SEQ ID NOs: 1-6, respectively, or that is an active portion thereof, that confer functionality; (2) Applicant has not taught the genus of structures having at least 95% sequence identity to SEQ ID NOs: 1-6 or active portion thereof, respectively (e.g., see sequence search results); (3) Applicant has not taught the structures of Cry2A, Cry1Ab and Cry1Bb that would result in functional activity; and (4) The specification teaches that TG event No. 49 had a particular insertion point that conferred resistance in eucalyptus however the Applicant has not taught all possible insertion points that would result in said phenotype.
This guidance is important because, for example, Guimarães et al. “Short-term evaluation in growing rats of diet containing Bacillus thuringiensis Cry1Ia12 entomotoxin: nutritional responses and some safety aspects” 2010, Journal of biomedicine & biotechnology vol. : 630267 (U) teaches that ribosomal proteins “express insecticidal genes (Cry genes) from Bacillus thuringiensis (Bt) stand out among the most commercialised. However, these genes confer resistance to major lepidopteran insect-pests [3] but are inefficient regarding the cotton boll weevil” … “[n]umerous data from toxicity studies have not shown any significant adverse effects of Cry proteins on mammals“ (pgs.1-2). Guimarães et al. teaches that Cry proteins do not target all pest even in the lepidopteran insect-pests genus.
The specification has not taught the conserved regions, motifs, features, or structures that are needed in order to confer Cry2A, Cry1Ab and Cry1Bb function or the synergistic effect of claim 14.
As such, and based on the state of the art, the nucleic and amino acid sequences and active portions thereof as encompassed by the claims may not yield plants with the trait as claimed or produce a synergistic effect on increasing resistance to an insect pest.
The issue with active portions thereof is that the specification does not adequately teach the size, region, location, motifs, or domains that would produce synergistic pesticidal activity. Therefore, one skilled in the art would not be able to predictably make a transgenic eucalyptus plant comprising a nucleic acid construct with only active portions that would result in synergistic pesticidal activity without undue experimentation.
Moreover, the specification has not provided working examples of the broad genus of sequences having at least 95% sequence identity to SEQ ID NO: 1-6 or active portions thereof retaining the functions of claims 2, 5, 13 and 14. Therefore, one skilled in the art would find it unpredictable which of these sequence variants having as little as 95% sequence identity would confer synergistic pesticidal activity in all pest. The amount of direction is insufficient to produce a plant with said phenotype with said construct without specifically teaching all the possible insertion sites without the need of undue experimentation.
Furthermore, claims 3, and 5 encompass a protein sequence having at least 95% identity to SEQ ID NO: 1, 3 and 5, or the amino acid sequence having at least 95% identity to SEQ ID NO: 2, 4 and 6. This requires the specification to provide guidance on the nucleic acid sequences encoding such proteins.
This requires the specification to teach the nucleic acid sequences encoding such proteins.
However, the specification does not teach or provide guidance for making a coding sequence having at least 95% identity to SEQ ID NO: 1, 3 and 5, or a polypeptide with at least 95% identity to SEQ ID NO: 2, 4 and 6, which leads to synergistic pesticidal activity.
A nucleic acid sequence having at least 95% identity to SEQ ID NOs: 2, 4 and 6 would have 95, 93 and 98 nucleic acid substitutions relative to SEQ ID NOs: 2, 4 and 6, respectively, while a polypeptide with at least 95% identity to SEQ ID NOs: 1, 3 and 5 would have 32, 31 and 33 amino acid substitutions relative to SEQ ID NOs: 1, 3 and 5, respectively.
These polynucleotide and polypeptides would encompass 395, 393 and 398 and 1932, 1931 and 1933 distinct gene and protein variants, respectively. In the absence of guidance indicating where in the sequence of SEQ ID NOs: 2, 4 and 6 such variations can be sustained, undue trial and error experimentation would be required to make the claimed polypeptide which would retain the activity of SEQ ID NO: 1, 3 and 5, and lead to the function of synergistic pest resistance.
The specification fails to teach the motifs, catalytic domains, etc. in these sequences that confers function and which predictably yields plants with the traits as claimed. Applicant has taught one structure/sequence which is not deemed enough working examples from the genus of sequences having 95% sequence identity to SEQ ID NO: 1-6, or active portions thereof that retain Cry2A, Cry1Ab and Cry1Bb protein function and in turn confer synergistic pest resistance.
This rationale and rejection also applies to the genus of sequences as encompassed by instant claim 8: the specification fails to teach a structure-function correlation for sequences that retain functional activity, fails to teach the domains or motifs needed for functional activity, and fails to provide working examples. All of this is critical because the art fails to teach or provide guidance for making a sequence with at least 90% sequence identity to SEQ ID NO: 36 that has rubisco promoter functional activity.
Additionally, the specification does not teach that all constructs expressing SEQ ID NOs:1-6 will confer synergistic pesticidal activity when transgenically integrated into the eucalyptus plant. The specification teaches synergistic pesticidal activity occurred only when certain conditions were met.
Specifically, the specification only teaches a particular insertion point (i.e., transgenic event No. 49 ) in Eucalyptus urophylla hybrid chromosome 3 short allele 420 base pairs upstream of the gene Eucgr.C03308. 1(pg. 36 table 7 and pg. 69 lines 19-30), yet the claim encompasses simultaneously expressing all three Cry proteins to produce synergistic pesticidal activity.
However, the specification teaches only one insertion point to achieve pesticidal phenotype. Therefore, the specification has not adequately provided guidance, and undue trial and error experimentation would be required to predictably produce a transgenic eucalyptus plant having synergistic pesticidal activity.
Given the breadth of the claims, the lack of sufficient guidance, the absence of working examples regarding structures that confer functional activity for Cry2A, Cry1Ab and Cry1Bb proteins and Cry2A, Cry1Ab and Cry1Bb proteins having at least 95% sequence identity to SEQ ID NOs:1-6 or active portions thereof, the state of the prior art which teaches that Cry proteins activity is not universal to have pesticidal activity in all pest, 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.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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.
Claims 1, 3, 5, 13-14 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Meade et al,. (WO 2011/075590 (N)), Pacheco et al. “Whole Genome Sequencing Analysis of Bacillus thuringiensis GR007 Reveals Multiple Pesticidal Protein Genes” 2021, Front. Microbiol. 12:758314. (V)) in view of Baum et al,. (US 11702455 B2 (A)).
In regard to claims 1, 3, 5 and 13-14, Meade et al. teach the concept of pyramid (stacking) multiple cry proteins in order to improve efficacy. Meade et al. teach the “combination of Cry1Ab and Cry2Aa to make plants (particularly corn or maize) more durable and less prone to allowing insects to develop that are resistant to the activity of either of these two toxins” (Title and para. [0005]).
Meade et al. teach that “[t]he subject invention also relates in part to triple stacks or "pyramids" of three (or more) protein toxins, with a Cry1Ab protein and a Cry2Aa protein being the base pair. (By "separate sites of action," it is meant that any of the given proteins do not cause cross-resistance with each other.) Adding a third protein that targets [European corn borer] ECB can provide a protein with a third site of action against ECB” (para. [0007]).
Meade et al. effectively utilizing a variety of Cry proteins that will target different avenues of attack to neutralize a pest and prevent resistance development (para. [0014]). Moreover, Meade et al. list additional insecticidal proteins that can be used in conjunction with Cry1Ab and Cry2Aa, see Appendix A on pgs. 17-30.
Meade et al. teach that “Cry2Aa and Cry1Ab are toxic to ECB larvae, yet they do not fully interact with the same receptor site(s); this shows that their toxicity will not be subject to cross-resistance in ECB” (para. [0015]).
Lastly, Meade et al. teach the sequence of Cry2Aa (GenBank accession No. AAA22335 as taught by Donovan, see p. 21), Cry1Ab (GenBank accession No. AAA22330 as taught by Wakibo, see p. 17) and Cry1Bb (GenBank accession No. AAA22344 as taught by Donovan, see p. 19) having 100% sequence identity to SEQ ID NO: 1, 3 and 5, respectively (see attachment below).
In regard to claim 18, Meade et al. teach producing a seed comprising the DNA encoding Cry1Ab and Cry2Aa (claim 4).
Meade et al. does not teach on specifically adding Cry1Bb to the stack, or teach eucalyptus plants comprising said proteins.
In regard to claims 1, 3 and 13-14, Pacheco et al. teach “[t]he Cry1Bb protein showed to be highly active against M. sexta with LC50 value of 5.4 ng/cm2 and this protein was the most active toxin against S. frugiperda among all tested proteins in this work, with a LC50 value of 128.5 ng/cm2 (Table 5), showing two times higher toxicity to S. frugiperda than previously reported” (pg. 10 col. 2 1st para.).
Additionally, Pacheco et al. teach “Cry1Bb, it was shown that this toxin and Cry1Fa share a binding site in the brush border membranes of S. frugiperda suggesting that Cry1Bb and Cry1Fa should show cross-resistance in this insect species” (pg. 10 col. Middle para.). In other words, Cry1Bb and Cry1Ab do not compete for the same receptor. This prevents pests from developing resistance to one Bt toxin, simultaneously becoming resistant to another, a process that would otherwise undermine "pyramided" (multi-toxin) crops designed to delay resistance. Therefore, Cry1B and Cry1Ab are compatible within a Cry protein stack and promoting a synergistic effect.
In regard to claims 1, 3 and 13-14, Baum et al. teach producing a transgenic eucalyptus plant (claim 7) comprising multiple Cry proteins to target lepidopteran pest (claims 3 and 12-13). Baum et al. teach that “[o]ne insect resistance management strategy is to employ transgenic crops that express two distinct insect inhibitory agents that operate through different modes of action. Therefore, any insects with resistance to either one of the insect inhibitory agents can be controlled by the other insect inhibitory agent” (sec. 17 line 30-37).
Therefore, prior to the effective filing date, it would have been prima facie obvious to one of ordinary skill in the art to combine the teachings of using Cry2Aa and Cry1Ab and third Cry protein as taught by Meade et al. and the teaching of the compatibility and effectiveness of Cry1Bb as taught by Pacheco et al. because Meade et al. specifically suggests using multiple Cry proteins and that would prevent pests from developing resistance to one Bt toxin, for example, as taught by Pacheco et al.
One would be motivated to do so in a eucalyptus plant because Baum et al. specifically teaches doing so and suggests using multiple Cry protein to target insect pests, and one would have a reasonable expectation of success because Meade et al. teaches the identical sequences as claimed, while each of Meade et al. and Pacheco et al. teach Cry proteins have their desired functionality.
One would have found it obvious to arrive at the nucleic acid sequences as encompassed by claim 5 because the amino acid sequences were known in the art, for example, as taught by Meade et al.
MPEP 2144.06 states that “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846”.
Thus, the choice of combining known insecticidal Bt toxins to produce synergistic pesticidal activity is an experimental design choice well within the means of one skilled in the art and would yield results with a reasonable expectation of success.
In regard to claim 18, one skilled in the art would have found it prima facie obvious and with a reasonable expectation of success to produce a plant seed comprising Cry2Aa, Cry1Ab and Cry1Bb because it would save time, money, and resources instead of producing another transgenic plant with said Cry proteins.
Conclusion
No claims are allowed.
Claims 8 and 56 appear to be free of the prior art. The closest prior art is discussed above but fails to reasonably teach suggest or provide motivation for using the promoter of SEQ ID NO: 36 or a plant characterized by SEQ ID NO: 48-56.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTIAN JOSE ORDAZ whose telephone number is (703)756-1967. The examiner can normally be reached 8:30 am-5:00 pm.
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/C.J.O./Examiner, Art Unit 1663
/JASON DEVEAU ROSEN/Primary Examiner, Art Unit 1662
ATTACHMENT
Alignment of SEQ ID NO: 1 and GenBank accession No. AAA22335 as taught by Meade and Donovan
LOCUS AAA22335 633 aa linear BCT 26-APR-1993
DEFINITION P2 crystal protein [Bacillus thuringiensis].
ACCESSION AAA22335
VERSION AAA22335.1
DBSOURCE locus BACCRYBI accession M31738.1
KEYWORDS .
SOURCE Bacillus thuringiensis
ORGANISM Bacillus thuringiensis
Bacteria; Bacillati; Bacillota; Bacilli; Bacillales; Bacillaceae;
Bacillus; Bacillus cereus group.
REFERENCE 1 (residues 1 to 633)
AUTHORS Donovan,W.P., Dankocsik,C.C., Gilbert,M.P., Gawron-Burke,M.C.,
Groat,R.G. and Carlton,B.C.
TITLE Amino acid sequence and entomocidal activity of the P2 crystal
protein. An insect toxin from Bacillus thuringiensis var. kurstaki
JOURNAL J. Biol. Chem. 263 (1), 561-567 (1988)
PUBMED 3121615
REMARK Erratum:[J Biol Chem 1989 Mar 15;264(8):4740]
REFERENCE 2 (residues 1 to 633)
AUTHORS Donovan,W.P., Dankocsik,C.C., Gilbert,M.P., Gawron-Burke,M.C.,
Groat,R.G. and Carlton,B.C.
TITLE Addition and corrections
JOURNAL J. Biol. Chem. 264, 4740-4740 (1989)
COMMENT Draft entry and computer readable sequence for [1] kindly provided
by W.Donovan, 25-NOV-1987.
Method: conceptual translation.
FEATURES Location/Qualifiers
source 1..633
/organism="Bacillus thuringiensis"
/db_xref="taxon:1428"
Protein 1..633
/name="P2 crystal protein"
Region 80..262
/region_name="Endotoxin_N"
/note="delta endotoxin, N-terminal domain; pfam03945"
/db_xref="CDD:397850"
Region 267..472
/region_name="Endotoxin_mid"
/note="Bacillus thuringiensis delta-Endotoxin, middle
domain; pfam09131"
/db_xref="CDD:117687"
Region 494..628
/region_name="Endotoxin_C"
/note="delta endotoxin; pfam03944"
/db_xref="CDD:397849"
CDS 1..633
/coded_by="M31738.1:156..2057"
/transl_table=11
GenCore version 6.5.2
Copyright (c) 1993 - 2026 Biocceleration Ltd.
OM protein - protein search, using sw model
Run on: April 11, 2026, 09:16:05 ; Search time 1 Seconds
(without alignments)
0.401 Million cell updates/sec
Title: US-18-837-818-1
Perfect score: 3306
Sequence: 1 MNNVLNSGRTTICDAYNVVA..........GTPFDLMNIMFVPTNLPPLY 633
Scoring table: BLOSUM62
Gapop 10.0 , Gapext 0.5
Searched: 1 seqs, 633 residues
Total number of hits satisfying chosen parameters: 1
Minimum DB seq length: 0
Maximum DB seq length: inf
Post-processing: Minimum Match 0%
Maximum Match 100%
Listing first 50 summaries
Database : AASEQ2_04112026_051550.fasta:*
SUMMARIES
%
Result Query
No. Score Match Length DB ID Description
----------------------------------------------------------------------------
1 3306 100.0 633 1 AASEQ2_04112026_051550
ALIGNMENTS
RESULT 1
AASEQ2_04112026_051550
Query Match 100.0%; Score 3306; DB 1; Length 633;
Best Local Similarity 100.0%;
Matches 633; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MNNVLNSGRTTICDAYNVVAHDPFSFEHKSLDTIQKEWMEWKRTDHSLYVAPVVGTVSSF 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MNNVLNSGRTTICDAYNVVAHDPFSFEHKSLDTIQKEWMEWKRTDHSLYVAPVVGTVSSF 60
Qy 61 LLKKVGSLIGKRILSELWGIIFPSGSTNLMQDILRETEQFLNQRLNTDTLARVNAELIGL 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 LLKKVGSLIGKRILSELWGIIFPSGSTNLMQDILRETEQFLNQRLNTDTLARVNAELIGL 120
Qy 121 QANIREFNQQVDNFLNPTQNPVPLSITSSVNTMQQLFLNRLPQFQIQGYQLLLLPLFAQA 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 QANIREFNQQVDNFLNPTQNPVPLSITSSVNTMQQLFLNRLPQFQIQGYQLLLLPLFAQA 180
Qy 181 ANMHLSFIRDVILNADEWGISAATLRTYRDYLRNYTRDYSNYCINTYQTAFRGLNTRLHD 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 ANMHLSFIRDVILNADEWGISAATLRTYRDYLRNYTRDYSNYCINTYQTAFRGLNTRLHD 240
Qy 241 MLEFRTYMFLNVFEYVSIWSLFKYQSLMVSSGANLYASGSGPQQTQSFTAQNWPFLYSLF 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 MLEFRTYMFLNVFEYVSIWSLFKYQSLMVSSGANLYASGSGPQQTQSFTAQNWPFLYSLF 300
Qy 301 QVNSNYILSGISGTRLSITFPNIGGLPGSTTTHSLNSARVNYSGGVSSGLIGATNLNHNF 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 QVNSNYILSGISGTRLSITFPNIGGLPGSTTTHSLNSARVNYSGGVSSGLIGATNLNHNF 360
Qy 361 NCSTVLPPLSTPFVRSWLDSGTDREGVATSTNWQTESFQTTLSLRCGAFSARGNSNYFPD 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 NCSTVLPPLSTPFVRSWLDSGTDREGVATSTNWQTESFQTTLSLRCGAFSARGNSNYFPD 420
Qy 421 YFIRNISGVPLVIRNEDLTRPLHYNQIRNIESPSGTPGGARAYLVSVHNRKNNIYAANEN 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 YFIRNISGVPLVIRNEDLTRPLHYNQIRNIESPSGTPGGARAYLVSVHNRKNNIYAANEN 480
Qy 481 GTMIHLAPEDYTGFTISPIHATQVNNQTRTFISEKFGNQGDSLRFEQSNTTARYTLRGNG 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 GTMIHLAPEDYTGFTISPIHATQVNNQTRTFISEKFGNQGDSLRFEQSNTTARYTLRGNG 540
Qy 541 NSYNLYLRVSSIGNSTIRVTINGRVYTVSNVNTTTNNDGVNDNGARFSDINIGNIVASDN 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 NSYNLYLRVSSIGNSTIRVTINGRVYTVSNVNTTTNNDGVNDNGARFSDINIGNIVASDN 600
Qy 601 TNVTLDINVTLNSGTPFDLMNIMFVPTNLPPLY 633
|||||||||||||||||||||||||||||||||
Db 601 TNVTLDINVTLNSGTPFDLMNIMFVPTNLPPLY 633
Search completed: April 11, 2026, 09:16:06
Job time : 2 secs
Alignment of SEQ ID NO: 3 and GenBank accession No. AAA22330 as taught by Meade and Wabiko
LOCUS AAA22330 1155 aa linear BCT 26-APR-1993
DEFINITION entomocidal protoxin [Bacillus thuringiensis].
ACCESSION AAA22330
VERSION AAA22330.1
DBSOURCE locus BACCRSB accession M13898.1
KEYWORDS .
SOURCE Bacillus thuringiensis
ORGANISM Bacillus thuringiensis
Bacteria; Bacillati; Bacillota; Bacilli; Bacillales; Bacillaceae;
Bacillus; Bacillus cereus group.
REFERENCE 1 (residues 1 to 1155)
AUTHORS Wabiko,H., Raymond,K.C. and Bulla,L.A. Jr.
TITLE Bacillus thuringiensis entomocidal protoxin gene sequence and gene
product analysis
JOURNAL DNA 5 (4), 305-314 (1986)
PUBMED 3743328
COMMENT A ribosome binding site is located at positions 131-136.
Method: conceptual translation.
FEATURES Location/Qualifiers
source 1..1155
/organism="Bacillus thuringiensis"
/db_xref="taxon:1428"
Protein 1..1155
/name="entomocidal protoxin"
Region 48..251
/region_name="Endotoxin_N"
/note="delta endotoxin, N-terminal domain; pfam03945"
/db_xref="CDD:397850"
Region 259..461
/region_name="Endotoxin_M"
/note="delta endotoxin; pfam00555"
/db_xref="CDD:395440"
Region 463..606
/region_name="delta_endotoxin_C"
/note="delta-endotoxin C-terminal domain may be associated
with carbohydrate binding functionality; cd04085"
/db_xref="CDD:271151"
Region 616..680
/region_name="Endotoxin_C2"
/note="Delta endotoxin; pfam18449"
/db_xref="CDD:436510"
Region 684..842
/region_name="Cry1Ac_D5"
/note="Insecticidal delta-endotoxin CryIA(c) domain 5;
pfam17997"
/db_xref="CDD:375474"
Region 876..>913
/region_name="Endotoxin_C2"
/note="Delta endotoxin; pfam18449"
/db_xref="CDD:436510"
CDS 1..1155
/coded_by="M13898.1:142..3609"
/transl_table=11
GenCore version 6.5.2
Copyright (c) 1993 - 2026 Biocceleration Ltd.
OM protein - protein search, using sw model
Run on: April 11, 2026, 09:15:29 ; Search time 1 Seconds
(without alignments)
0.718 Million cell updates/sec
Title: US-18-837-818-3
Perfect score: 3240
Sequence: 1 MDNNPNINECIPYNCLSNPE..........EFVPAEVTFEAEYDLERAQK 622
Scoring table: BLOSUM62
Gapop 10.0 , Gapext 0.5
Searched: 1 seqs, 1155 residues
Total number of hits satisfying chosen parameters: 1
Minimum DB seq length: 0
Maximum DB seq length: inf
Post-processing: Minimum Match 0%
Maximum Match 100%
Listing first 50 summaries
Database : AASEQ2_04112026_051409.fasta:*
SUMMARIES
%
Result Query
No. Score Match Length DB ID Description
----------------------------------------------------------------------------
1 3240 100.0 1155 1 AASEQ2_04112026_051409
ALIGNMENTS
RESULT 1
AASEQ2_04112026_051409
Query Match 100.0%; Score 3240; DB 1; Length 1155;
Best Local Similarity 100.0%;
Matches 622; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MDNNPNINECIPYNCLSNPEVEVLGGERIETGYTPIDISLSLTQFLLSEFVPGAGFVLGL 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MDNNPNINECIPYNCLSNPEVEVLGGERIETGYTPIDISLSLTQFLLSEFVPGAGFVLGL 60
Qy 61 VDIIWGIFGPSQWDAFLVQIEQLINQRIEEFARNQAISRLEGLSNLYQIYAESFREWEAD 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 VDIIWGIFGPSQWDAFLVQIEQLINQRIEEFARNQAISRLEGLSNLYQIYAESFREWEAD 120
Qy 121 PTNPALREEMRIQFNDMNSALTTAIPLFAVQNYQVPLLSVYVQAANLHLSVLRDVSVFGQ 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 PTNPALREEMRIQFNDMNSALTTAIPLFAVQNYQVPLLSVYVQAANLHLSVLRDVSVFGQ 180
Qy 181 RWGFDAATINSRYNDLTRLIGNYTDHAVRWYNTGLERVWGPDSRDWIRYNQFRRELTLTV 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 RWGFDAATINSRYNDLTRLIGNYTDHAVRWYNTGLERVWGPDSRDWIRYNQFRRELTLTV 240
Qy 241 LDIVSLFPNYDSRTYPIRTVSQLTREIYTNPVLENFDGSFRGSAQGIEGSIRSPHLMDIL 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 LDIVSLFPNYDSRTYPIRTVSQLTREIYTNPVLENFDGSFRGSAQGIEGSIRSPHLMDIL 300
Qy 301 NSITIYTDAHRGEYYWSGHQIMASPVGFSGPEFTFPLYGTMGNAAPQQRIVAQLGQGVYR 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 NSITIYTDAHRGEYYWSGHQIMASPVGFSGPEFTFPLYGTMGNAAPQQRIVAQLGQGVYR 360
Qy 361 TLSSTLYRRPFNIGINNQQLSVLDGTEFAYGTSSNLPSAVYRKSGTVDSLDEIPPQNNNV 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 TLSSTLYRRPFNIGINNQQLSVLDGTEFAYGTSSNLPSAVYRKSGTVDSLDEIPPQNNNV 420
Qy 421 PPRQGFSHRLSHVSMFRSGFSNSSVSIIRAPMFSWIHRSAEFNNIIPSSQITQIPLTKST 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 PPRQGFSHRLSHVSMFRSGFSNSSVSIIRAPMFSWIHRSAEFNNIIPSSQITQIPLTKST 480
Qy 481 NLGSGTSVVKGPGFTGGDILRRTSPGQISTLRVNITAPLSQRYRVRIRYASTTNLQFHTS 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 NLGSGTSVVKGPGFTGGDILRRTSPGQISTLRVNITAPLSQRYRVRIRYASTTNLQFHTS 540
Qy 541 IDGRPINQGNFSATMSSGSNLQSGSFRTVGFTTPFNFSNGSSVFTLSAHVFNSGNEVYID 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 IDGRPINQGNFSATMSSGSNLQSGSFRTVGFTTPFNFSNGSSVFTLSAHVFNSGNEVYID 600
Qy 601 RIEFVPAEVTFEAEYDLERAQK 622
||||||||||||||||||||||
Db 601 RIEFVPAEVTFEAEYDLERAQK 622
Search completed: April 11, 2026, 09:15:29
Job time : 1 secs
Alignment of SEQ ID NO: 5 and GenBank accession No. AAA22344 as taught by Meade and Donovan
LOCUS AAA22344 1229 aa linear BCT 25-APR-1994
DEFINITION crystal protein [Bacillus thuringiensis].
ACCESSION AAA22344
VERSION AAA22344.1
DBSOURCE locus BACCRYIE accession L32020.1
KEYWORDS .
SOURCE Bacillus thuringiensis
ORGANISM Bacillus thuringiensis
Bacteria; Bacillati; Bacillota; Bacilli; Bacillales; Bacillaceae;
Bacillus; Bacillus cereus group.
REFERENCE 1 (residues 1 to 1229)
AUTHORS Donovan,W.P.
JOURNAL Unpublished
COMMENT Method: conceptual translation.
FEATURES Location/Qualifiers
source 1..1229
/organism="Bacillus thuringiensis"
/strain="EG 5847"
/db_xref="taxon:1428"
Protein 1..1229
/product="crystal protein"
/function="insect toxin"
Region 72..275
/region_name="Endotoxin_N"
/note="delta endotoxin, N-terminal domain; pfam03945"
/db_xref="CDD:397850"
Region 283..495
/region_name="Endotoxin_M"
/note="delta endotoxin; pfam00555"
/db_xref="CDD:395440"
Region 496..639
/region_name="delta_endotoxin_C"
/note="delta-endotoxin C-terminal domain may be associated
with carbohydrate binding functionality; cd04085"
/db_xref="CDD:271151"
Region 649..713
/region_name="Endotoxin_C2"
/note="Delta endotoxin; pfam18449"
/db_xref="CDD:436510"
Region 739..919
/region_name="Cry1Ac_D5"
/note="Insecticidal delta-endotoxin CryIA(c) domain 5;
pfam17997"
/db_xref="CDD:375474"
Region 953..1025
/region_name="Endotoxin_C2"
/note="Delta endotoxin; pfam18449"
/db_xref="CDD:436510"
CDS 1..1229
/gene="cryI ET5"
/coded_by="L32020.1:67..3756"
/transl_table=11
GenCore version 6.5.2
Copyright (c) 1993 - 2026 Biocceleration Ltd.
OM protein - protein search, using sw model
Run on: April 11, 2026, 09:13:44 ; Search time 1 Seconds
(without alignments)
0.805 Million cell updates/sec
Title: US-18-837-818-5
Perfect score: 3427
Sequence: 1 MTSNRKNENEIINALSIPTV..........EFVPAEVTFEAEYDLERAQK 655
Scoring table: BLOSUM62
Gapop 10.0 , Gapext 0.5
Searched: 1 seqs, 1229 residues
Total number of hits satisfying chosen parameters: 1
Minimum DB seq length: 0
Maximum DB seq length: inf
Post-processing: Minimum Match 0%
Maximum Match 100%
Listing first 50 summaries
Database : AASEQ2_04112026_051322.fasta:*
SUMMARIES
%
Result Query
No. Score Match Length DB ID Description
----------------------------------------------------------------------------
1 3427 100.0 1229 1 AASEQ2_04112026_051322
ALIGNMENTS
RESULT 1
AASEQ2_04112026_051322
Query Match 100.0%; Score 3427; DB 1; Length 1229;
Best Local Similarity 100.0%;
Matches 655; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MTSNRKNENEIINALSIPTVSNPSTQMNLSPDARIEDSLCVAEVNNIDPFVSASTVQTGI 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MTSNRKNENEIINALSIPTVSNPSTQMNLSPDARIEDSLCVAEVNNIDPFVSASTVQTGI 60
Qy 61 NIAGRILGVLGVPFAGQLASFYSFLVGELWPSGRDPWEIFLEHVEQLIRQQVTENTRNTA 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 NIAGRILGVLGVPFAGQLASFYSFLVGELWPSGRDPWEIFLEHVEQLIRQQVTENTRNTA 120
Qy 121 IARLEGLGRGYRSYQQALETWLDNRNDARSRSIILERYVALELDITTAIPLFRIRNEEVP 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 IARLEGLGRGYRSYQQALETWLDNRNDARSRSIILERYVALELDITTAIPLFRIRNEEVP 180
Qy 181 LLMVYAQAANLHLLLLRDASLFGSEWGMASSDVNQYYQEQIRYTEEYSNHCVQWYNTGLN 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 LLMVYAQAANLHLLLLRDASLFGSEWGMASSDVNQYYQEQIRYTEEYSNHCVQWYNTGLN 240
Qy 241 NLRGTNAESWLRYNQFRRDLTLGVLDLVALFPSYDTRTYPINTSAQLTREIYTDPIGRTN 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 NLRGTNAESWLRYNQFRRDLTLGVLDLVALFPSYDTRTYPINTSAQLTREIYTDPIGRTN 300
Qy 301 APSGFASTNWFNNNAPSFSAIEAAIFRPPHLLDFPEQLTIYSASSRWSSTQHMNYWVGHR 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 APSGFASTNWFNNNAPSFSAIEAAIFRPPHLLDFPEQLTIYSASSRWSSTQHMNYWVGHR 360
Qy 361 LNFRPIGGTLNTSTQGLTNNTSINPVTLQFTSRDVYRTESNAGTNILFTTPVNGVPWARF 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 LNFRPIGGTLNTSTQGLTNNTSINPVTLQFTSRDVYRTESNAGTNILFTTPVNGVPWARF 420
Qy 421 NFINPQNIYERGATTYSQPYQGVGIQLFDSETELPPETTERPNYESYSHRLSHIGLIIGN 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 NFINPQNIYERGATTYSQPYQGVGIQLFDSETELPPETTERPNYESYSHRLSHIGLIIGN 480
Qy 481 TLRAPVYSWTHRSADRTNTIGPNRITQIPLVKALNLHSGVTVVGGPGFTGGDILRRTNTG 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 TLRAPVYSWTHRSADRTNTIGPNRITQIPLVKALNLHSGVTVVGGPGFTGGDILRRTNTG 540
Qy 541 TFGDIRLNINVPLSQRYRVRIRYASTTDLQFFTRINGTTVNIGNFSRTMNRGDNLEYRSF 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 TFGDIRLNINVPLSQRYRVRIRYASTTDLQFFTRINGTTVNIGNFSRTMNRGDNLEYRSF 600
Qy 601 RTAGFSTPFNFLNAQSTFTLGAQSFSNQEVYIDRVEFVPAEVTFEAEYDLERAQK 655
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 RTAGFSTPFNFLNAQSTFTLGAQSFSNQEVYIDRVEFVPAEVTFEAEYDLERAQK 655
Search completed: April 11, 2026, 09:13:44
Job time : 1 secs
Prosecution Insights