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 .
Status of the Claims
Claims 1-3, 6-19 are pending.
Claims 1-3, 6-19 are examined herein.
Election/Restrictions
Applicant’s election of the species of SEQ ID NO:6 in the reply filed on 07/24/2024 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Priority
Applicant’s claim for the benefit of prior-filed applications under 35 U.S.C. § 119(e) or under 35 U.S.C. §§ 120, 121, or 365(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of some of the earlier
filing dates under 35 U.S.C. §§ 119(e) and 120 as follows:
No certified copy or certified translation of the foreign priority documents have been received. As such, any claim to foreign priority is not recognized.
Claim Interpretation
Claims 1, 6, 10-11, 13-15, and 17-19 recite “as show in” followed by SEQ ID NOs. Because the term “as shown in” reasonably encompasses fragments, the claims are interpreted to include both fragments of the sequences and the full length sequences. If Applicant intends for the ACe1 protein of the invention to be limited to the full length of the claimed sequences, Applicant can amend the claims to recite “having the amino acid sequence of SEQ ID NOs…”.
Claim 7 recites “the transgenic plant further comprises at least one second nucleotide different from the nucleotide encoding the ACe1 protein”. Because dependent claims 8 and 9 describe the second nucleotide to encode a protein, claim 7 is interpreted as requiring a second nucleotide sequence that is different from the nucleotide sequence encoding the ACe1 protein.
Claim Objections
In claims 1, 6-7, and 13-19, “ACe1” is used as abbreviation. It is suggested to insert a definition for ACe1 without bringing in new matter, immediately before the first appearance of “ACe1” in claim 1; and to enclose the appearance of “ACe1” in parentheses (in claim 1 only).
Claim 19 recites “…wherein the ACh1 protein…”. Applicant should amend ACh1 to ACe1.
Claim Rejections - 35 USC § 112
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 and 6-19 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 ACe1 protein is an essential element of the claims. Applicant describes ACe1 protein as a new class of insecticidal proteins which are completely different from Bt proteins, and are speculated to be a β-pore forming protein (specification, page 4). Applicant described the mechanism of action is generally enzymatic cleavage activation, binding with receptors, formation of oligomers, and pore-forming on membrane surfaces (specification, page 4). Applicant discloses that the protein must be digested to form an active protein and cleavage is mainly at the amino-terminal or carboxyl-terminal turns the protein into an active fragment that binds a receptor on an epithelial cell membrane, which produces lesions, disrupts digestion, and causes death of the insect. Applicant described SEQ ID NOs: 1-8, 10-11, 13-15 as representative of the claimed genus (specification, page 5, and claim 1).
Palma (Palma et al. (2014) Bacillus thuringiensis toxins: an overview of their biocidal activity. Toxins, 6(12), 3296-3325) teaches about Bacillus thuringiensis (Bt) toxins, the wide diversity of Bt proteins, and their biocidal activity (Title, entire document). Palma teaches some of the Bt proteins are Cry toxins that are pore-forming, and two domains of the protein consist of β-sheets that are involved in receptor binding and pore-formation (page 3301, paragraph 3) (i.e. β -pore forming as described in the specification). Palma also teaches the mode of action has been studied mainly in Lepidopteran insects (Ostrinia furnacalis of the instant application is a species of the order Lepidoptera), and includes: (a) crystal inclusion ingestion and dissolution in the alkaline midgut lumen; (b) protoxin (native protein) proteolytic activation that turns the native Cry protein into smaller protease-resistant toxic polypeptides; (c) binding of toxin fragments to specific receptors on the surface of midgut epithelial cells; and (d) formation of non-selective pores which produce the lysis of epithelial cells and hence midgut disarrangements, leading to insect death (page 3302, paragraphs 2-3, page 3303, paragraph 1).
Based on what is known in the art and what is provided by the Applicant in the specification, the relationship between the structure of ACe1 proteins and the functions of the proteins (completely different from Bt proteins, and are speculated to be a β-pore forming protein) is not described by the prior art and the instant disclosure fails to remedy this deficiency. As such, one of ordinary skill in the art would not have been able to distinguish a polypeptide that structurally resembled a Bt toxin from an ACe1 polypeptide as encompassed by the claims or something else.
Although applicant has provided 13 different exemplar species of the genus (SEQ ID NOs: 1-8, 10-11, 13-15), this is insufficient to describe the genus by virtue of example, given the unknown, potentially vast size of the genus. One of ordinary skill in the art would not have recognized that Applicant was in possession of the recited genus.
Indefiniteness
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-3 and 6-19 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 contain a limitation that overcomes the deficiencies of the parent claim from which they depend.
Regarding claim 1, 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 1 recites the broad recitation of “a method for controlling Ostrinia furnacalis (Hubern), comprising allowing the Ostrinia furnacalis (Hubern) to be at least in contact with an ACe1 protein”, and the claim also recites i) preferably, the ACe1 protein is present in a host cell that produces at least the ACe1 protein, and the Ostrinia furnacalis (Hubern) is in contact with at least the ACe1 protein by ingesting the host cell and ii) more preferably, the ACe1 protein is present in bacteria or a transgenic plant that produces at least the ACe1 protein, the Ostrinia furnacalis (Hubern) is in contact with at least the ACe1 protein by ingesting the bacterium or tissue of the transgenic plant, and after contacting, the growth of the Ostrinia furnacalis (Hubern) is inhibited and/or death is caused, so as to achieve the control of the damage of the Ostrinia furnacalis (Hubern) to plants, which are the narrower statements of the range/limitation. The claim(s) are 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.
Claims 1, 13, and 16 recite the term “ACe1” which is indefinite. Applicant states ACe1 is a new class of insecticidal proteins completely different from the traditional Bt protein (specification, page 4, paragraph 4). However, sequence searches show that SEQ ID NO:6, for example, is an endotoxin related to Bt endotoxins (NCBI Blast Accession No. WP_022584503), and the instant disclosure does not make clear where the division between ACe1 polypeptides and other endotoxins is. Additionally, the term ACe1 is not a term commonly used in the art, and without further definitions specifying the structure of said ACe1, one of ordinary skill in the art would not be apprised of what the term means. For purposes of examination, the term is reasonably interpreted to encompass any endotoxin that has sequence identity to the recited sequence identifiers. This interpretation does not relieve Applicant of the duty to amend the claims to address the identified deficiency.
Claims 6, 14, 15, 18, and 19 recite “the polynucleotide sequence of the ACe1 protein…” or “the ACe1 protein has a nucleotide sequence…”. Applicant’s claims present contradictory language. A protein does not have a nucleotide sequence – it has an amino acid sequence. As such it is unclear if Applicant intended the claim to require the cited nucleotide sequence or some other sequence. As such the metes and bounds of the claims are unclear. For purposes of examination, the claims are interpreted to mean that the recited nucleotide sequence encodes the polypeptide. This interpretation does not relieve Applicant of the duty to amend the claims to address the identified deficiency.
Claims 7 recites the limitation "one second nucleotide different from the nucleotide encoding the ACe1 protein". The term nucleotide in “One second nucleotide” and “the nucleotide” is interpreted as a single nucleotide. However, a single nucleotide does not encode a protein. It is suggested to change the term “nucleotide” in both instances in the claim to “polynucleotide sequence”; cf. claim 17.
Claims 8 and 9 recite the limitation "the second nucleotide encodes…". The term nucleotide in is interpreted as a single nucleotide. However, a single nucleotide does not encode a protein. It is suggested to change the term “nucleotide” in the claims to “polynucleotide sequence”; cf. claim 17.
Claim 8 also recites “Cry-like” and “Vip-like”. The applicant has not defined “-like” in the specification and the addition of “-like” is an equivalent of “or the like”. The phrase "or the like" renders the claim(s) indefinite because the claim(s) include(s) elements not actually disclosed (those encompassed by "or the like"), thereby rendering the scope of the claim(s) unascertainable. See MPEP § 2173.05(d). It is suggested that the Applicant defines “Cry-like” and “Vip-like” in the specification without adding new matter, or remove “-like” from the claim.
Claim 12 recites the term “important”, which is a relative term and renders the claim indefinite. The term “important” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Specifically, the term “important”, which refers to a gene, can mean different things among various persons of ordinary skill. In light of the specification, important seems to mean a gene is required for insect growth and/ or survival. However, there are other genes that may be considered important, for example OBP genes can influence insect food preferences (See Kohlmeier et al. (2023). Genetic mechanisms modulating behaviour through plastic chemosensory responses in insects. Molecular Ecology, 32(1), 45-60).
Claim 17 also recites the limitation "the hazard" in line 7 of the claim. There is insufficient antecedent basis for this limitation in the claim, as there is no previous mention of “hazard” in the claim. It is suggested to change “the” to ---a---.
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.
Claims 1-3, 13, and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Cao et al. (CN-113186194-A) (herein referred to Cao), Bean et al. (WO-2016081618-A1) (herein referred to as Bean), and Tan et al. (Tan et al., 2011, Comparative susceptibility of Ostrinia furnacalis, Ostrinia nubilalis and Diatraea saccharalis (Lepidoptera: Crambidae) to Bacillus thuringiensis Cry1 toxins. Crop protection, 30(9), 1184-1189) (herein referred to as Tan).
Regarding claim 1, Cao teaches a method of controlling Ostrinia furnacalis (Abstract), comprising a protein present in a transgenic plant that expresses the protein (paragraph n0047); ingestion of the transgenic plant by the Asian corn borer (i.e. Ostrinia furnacalis) (paragraph n0047); and after ingesting the toxic protein, the protein causes growth inhibition of the insect (i.e. Ostrinia furnacalis) (paragraph n0041), so as to achieve the control the Asian corn borer and protect crops (Abstract, paragraph n0046).
Cao does not teach the protein is an ACe1 protein, and wherein the ACe1 protein is ACe1_9 protein (SEQ ID NO 6).
In a related invention, Bean teaches transgenic plants expressing insecticidal proteins that exhibit toxic activity against Lepidopteran pests (abstract), including Ostrinia nubilalis (paragraphs 0105, 0108, and 0170). Specifically, Bean teaches the protein of TIC3668 (SEQ ID NO: 2 of Bean), which has an identical fragment to SEQ ID NO: 6 of the instant application (see Figure 1 below for alignment) that causes stunting and mortality in Western European Corn Borer (i.e. “ECB” or Ostrinia nubilalis) (paragraph 0170, Table 9 of Bean). Tan teaches Ostrinia furnacalis and Ostrinia nubilalis are closely related (abstract), very similar in biology and morphology, and share a primary preference for corn as its host (page 1185, paragraph 2).
It would therefore have been obvious to a person of ordinary skill in the art to
have combined the method as taught by Cao with the teachings of Bean and Tan to arrive at the instantly claimed method with a reasonable expectation of success
for the purpose of controlling Lepidopteran species pests using the insecticidal protein as taught by Bean (abstract), and for the purpose of applying existing data regarding Ostrinia nubilalis to Ostrinia furnacalis as taught by Tan (page 1185, paragraph 3, page 1188, paragraph 6).
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Figure 1. Alignment of SEQ ID NO:6 of the instant application (i.e. Query line) to SEQ ID NO:2 of Bean (i.e. Subject line). Alignment shows 100% identity of a fragment of SEQ ID NO:6 of the instant application to SEQ ID NO:2 of Bean (indicated by red underline).
Regarding claim 2, Cao teaches the transgenic plant is corn (paragraph n0012 and n0049).
Regarding claim 3, Cao teaches the nucleotide sequence encoding the protein is in the leaf (paragraph n0052).
Regarding claim 13, Cao teaches a method of producing pest-resistant plants, the method comprising introducing a polynucleotide encoding a protein into a plant (paragraph n0080).
Regarding claim 16, Cao teaches crossing (i.e. hybridizing) a first plant the chimeric gene, recombinant vector, expression cassette or nucleic acid molecule with a second, different plant to obtain offspring plants (i.e. produce seed) expressing all the genes introduced into the parent plants (paragraphs n0079-n0080)
Claims 17 is rejected under 35 U.S.C. 103 as being unpatentable over Baum et al. (US Patent Application Publication US 2013/0269060 A1) (herein referred to as Baum), Bean et al. (WO-2016081618-A1) (herein referred to as Bean), and Tan et al. (Tan et al., 2011, Comparative susceptibility of Ostrinia furnacalis, Ostrinia nubilalis and Diatraea saccharalis (Lepidoptera: Crambidae) to Bacillus thuringiensis Cry1 toxins. Crop protection, 30(9), 1184-1189) (herein referred to as Tan).
Regarding claim 17, Baum teaches an invention related to proteins exhibiting insect inhibitory activity against agriculturally relevant pests (paragraph 0003) and describes pore-forming loops (paragraph 0091), which is similarly described in the instant application (page 4, paragraph 4-5). In this invention, Baum teaches planting 30 seeds per transgenic plant (paragraph 0114) (i.e. planting at least one plant seed); a transgenic plant seed comprising a polynucleotide sequence encoding a protein (i.e. the plant seed comprises the polynucleotide sequence encoding a protein); growing the planted seeds to flowering (paragraph 0114) (i.e. growing the plant seed into a plant); conducting field trials with the plants under natural pest pressures (paragraphs 0115-0116) (i.e. growing the plant under conditions that the pest naturally occurs); and results showed yield of the transgenic plants was higher compared to the non-transgenic control (i.e. harvesting a plant that has an increased plant yield compared with other plants that do not have the polynucleotide sequence encoding the protein of interest) (paragraph 0116).
Baum does not teach:
the protein is an Ace_1 protein, wherein the ACe1 protein is an ACe1_9 protein
the pest is Ostrinia furnacalis
In a related invention, Bean teaches transgenic plants expressing insecticidal proteins that exhibit toxic activity against Lepidopteran pests (abstract), including Ostrinia nubilalis (paragraphs 0105, 0108, and 0170). Specifically, Bean teaches the protein of TIC3668 (SEQ ID NO: 2 of Bean), which has an identical fragment to SEQ ID NO: 6 of the instant application (see Figure 1 below for alignment) that causes stunting and mortality in Western European Corn Borer (i.e. “ECB” or Ostrinia nubilalis) (paragraph 0170, Table 9 of Bean). Tan teaches Ostrinia furnacalis and Ostrinia nubilalis are closely related (abstract), very similar in biology and morphology, and share a primary preference for corn as its host (page 1185, paragraph 2).
It would therefore have been obvious to a person of ordinary skill in the art to
have combined the method as taught by Baum with the teachings Bean and Tan to arrive at the instantly claimed method with a reasonable expectation of success
for the purpose of controlling Lepidopteran species pests using the insecticidal protein as taught by Bean (abstract), and for the purpose of applying existing data regarding Ostrinia nubilalis to Ostrinia furnacalis as taught by Tan (page 1185, paragraph 3, page 1188, paragraph 6).
Conclusion
No claims are allowed.
Claims 6-12, 14-15, and 18-19 appear to be provisionally free of the prior art, relative to the nucleotide sequences (SEQ ID NOs: 24 and 48) that correspond with elected species Ace1_9 protein (SEQ ID NO: 6) examined herein, pending receipt of information requested under 37 CFR § 1.105 (see below). While the art teaches the general concept of controlling a Lepidopteran pest by allowing the pest to be in contact with a fragment of the TIC3668 (i.e., ACe1) protein, the instantly claimed nucleotide SEQ ID NOs: 24 and 48 do not expressly appear in the art.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JESSICA N STOCKDALE whose telephone number is (703)756-5395. The examiner can normally be reached M-F 7:30-5 ET, off first Friday.
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JESSICA N. STOCKDALE
Examiner
Art Unit 1663
/JESSICA NICOLE STOCKDALE/Examiner, Art Unit 1663
/CHARLES LOGSDON/Primary Examiner, Art Unit 1662
Request for Information under 37 CFR § 1.105
Applicant and the assignee of this application are required under 37 CFR § 1.105 to provide the following information that the examiner has determined is reasonably necessary to the examination of this application.
This request is being made for the following reasons:
Applicant is claiming a method of controlling Ostrinia furnacalis by contacting the pest with an ACe1 protein, in some embodiments having an amino acid residue sequence of one of SEQ ID NO:1-8, 10-11, or 13-15. In further embodiments, the protein is encoded by sequences for expression in bacteria (SEQ ID NO:19-26, 28-29, 31-33) or plants (SEQ ID NO:43-50, 52-53, 55-57).
However, the instant Specification is silent as to how Applicant obtained the nucleotide sequences of SEQ ID NO: 19-26, 28-29, 31-33 or 43-50, 52-53, 55-57. The source of these sequences is important for determining patentability. The information requested herein is required to make a meaningful and complete search of the prior art.
In response to this requirement, if known, please provide answers to each of the following interrogatories eliciting factual information:
(i) Please supply the source of the nucleotide sequences of SEQ ID NO: 19-26, 28-29, 31-33 or 43-50, 52-53, 55-57. If said sequences were obtained from an organism, identify the organism by species name and strains where applicable. If the sequences were artificially generated, explain how this was done including whether any codon-optimization tables or tools were used, what those tables or tools were and whether said tables or tools are publicly accessible and if so, where they can be accessed.
If Applicant views any or all of the above requested information as a Trade Secret, then Applicant should follow the guidance of MPEP § 724.02 when submitting the requested information.
In responding to those requirements that require copies of documents, where the document is a bound text or a single article over 50 pages, the requirement may be met by providing copies of those pages that provide the particular subject matter indicated in the requirement, or where such subject matter is not indicated, the subject matter found in applicant’s disclosure. Please indicate where the relevant information can be found.
The fee and certification requirements of 37 CFR § 1.97 are waived for those documents submitted in reply to this requirement. This waiver extends only to those documents within the scope of this requirement under 37 CFR § 1.105 that are included in the applicant’s first complete communication responding to this requirement. Any supplemental replies subsequent to the first communication responding to this requirement and any information disclosures beyond the scope of this requirement under 37 CFR § 1.105 are subject to the fee and certification requirements of 37 CFR § 1.97 if submitted subsequent to a first Office action on the merits.
The applicant is reminded that the reply to this requirement must be made with candor and good faith under 37 CFR § 1.56. Where the applicant does not have or cannot readily obtain an item of required information, a statement that the item is unknown or cannot be readily obtained may be accepted as a complete reply to the requirement for that item.
This requirement is an attachment of the enclosed Office action. A complete reply to the enclosed Office action must include a complete reply to this requirement.
The time period for reply to this requirement coincides with the time period for reply to the enclosed Office action.
/Amjad Abraham/SPE, Art Unit 1663