DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant's election with traverse of Group II in the reply filed on 5/27/2026 is acknowledged. The Applicant also elects, with traverse, the following species.
SEQ ID species - SEQ ID NO: 10
Insect species - Fall armyworm (FAW) (Spodoptera frugiperda)
Plant species - maize (corn)
The traversal is on the grounds that “The pending claims are directed to a single general inventive concept centered on recombinant nucleic acids encoding pesticidal polypeptides and their use in biological systems. The nucleic acids of Group II are directly implemented in the plant (Group I) and cell (Group III) embodiments. These groups are therefore functionally and structurally linked, and do not constitute independent or distinct inventions” (response, p.6, para 3) and “The core foundation across all claims groups centers on the same nucleic acid sequences, encoded polypeptides, and pesticidal activity, such that substantial overlap in search and examination would be expected” (response, p.6, para 5).
This is not found persuasive because the inventions separated in different Groups are distinct from the other because they satisfy at least one criterion, as described in the previous Office action (dated 4/29/2026, page 2-4). The inventions of group I needs a plant to be transformed and produce seeds which are not present in the inventions of Group II or Group III. As such, searches for the three inventions would not be extensive and would be a search and/or examination burden.
Moreover, the groups also belong to different CPC classification as described in the previous Office action (dated 4/29/2026, p.2).
Regarding the election of species for a sequence identifier: the elected species of SEQ ID NO: 10, when operably linked to a heterologous promoter that directs expression in plant tissue, was found free of the prior art. Therefore, in compliance with MPEP 803.02(III)(C)(2), a search was expanded to further species. All of SEQ ID NOs: 1, 2, 4-8, 10, 12, 15, 21-25, and 29-34, when operably linked to a heterologous promoter that directs expression in plant tissue, were rejoined and found free of the prior art. The
The requirement is still deemed proper and is therefore made FINAL.
Claim Status
Claims 1-24 are pending.
Claims 1-5, 12-13, 17-18, and 20-24 are withdrawn from examination as being part of non-elected Groups.
Claims 6-11, 14-16 and 19 are being examined.
Claim Rejections - 35 USC § 112(a)
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.
Written Description
Claims 6-10 and 14-16 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 claims contain 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.
Claim 6 and 14 are drawn to a recombinant nucleic acid molecule operably linked to one or more heterologous promoter sequences that direct expression in plant tissue and encoding a polypeptide having at least 95% sequence identity to any one of SEQ ID NOs: 1, 2, 4-8, 10, 12, 15, 21- 25, and 29-34, wherein the polypeptide has pesticidal activity against a plant pathogen or pest.
The Applicant describes identifying a novel polypeptide sequence (SEQ ID NO: 1) comprising insecticidal activity (spec, p.33, para 000116, line 1-2) and then created variants (SEQ ID NO: 2-56) with increased insecticidal activity, altered spectrum of insecticidal activity, increased durability, or increased stability (spec, p.33, para 000116, line 2-4). Different proteins are expressed in either E coli (spec, p. 33, Example 2, line 1-2) or in transiently expressed in Nicotiana benthamiana to identify specific insecticidal activity (spec, p. 36, para 000122, line 1-2). The results of insecticidal activity of various proteins are summarized in Table 1 and Table 2. Table 1 describes insecticidal activity of E coli expressed proteins against specific insect pests viz Fall armyworm (FAW, Spodoptera frugiperda), European corn borer (ECB, Ostrinia nubilalis), sugarcane borer (SCB, Diatraea saccharalis) and western corn rootworm (WCR, Diabrotica virgifera virgifera) (spec, p. 34, Table 1, para 000121). Table 2 describes insecticidal activity of transiently expressed proteins in tobacco (Nicotiana benthamiana) leaves against specific insect pests viz. Fall armyworm (FAW), European corn borer (ECB), sugarcane borer (SCB), corn earworm (CEW, Helicoverpa zea,) and soybean looper (SBL, Chrysodeixis includens) (spec, p.37, Table 2, para 000123).
Not all the claimed polypeptide sequences (SEQ ID NOs: 1, 2, 4-8, 10, 12, 15, 21- 25, and 29-34) are tested by the Applicant against representative species of all available plant pathogens or pests that would include virus, bacteria, fungi, bacteria, nematodes, mites, ticks etc. besides insect pests. The specification shows in Table 1 that the polypeptide set forth in SEQ ID NO: 23 does not show any pesticidal activity against any plant pathogen or pest when expressed in E coli. Table 2 shows that SEQ ID NOs: 6, 7 and 10 do not show any activity when expressed in a plant leaf. The other sequences (SEQ ID NOs: 12, 15, 21-25 and 29-34) encompassed by the claims are not even tested in a plant tissue. It is also noted in Table 2 that SEQ ID NO: 1 is expressed in a plant leaf assay, using different expression cassettes, which gave different results. It is unclear what the differences are between these cassettes, and how they affect the activity of SEQ ID NO: 1 in the assay. It is unclear whether a particular plant-expressible promoter, other regulatory element(s), or the expressed sequence itself, is/are necessary for pesticidal activity in a plant.
Moreover, the Applicant does not describe any structure function relationship of these novel proteins in respect to its specific insecticidal activities while claiming the broad genus of pesticidal activity against any plant pathogen or any plant pest. There is no specific domain or amino acid sequence assigned to the specific and novel insecticidal activity. A skilled artisan would not be able to mutate up to 14 amino acids, i.e., 5% of the (about 285) amino acid long polypeptides, anywhere along the entire length of the proteins while retaining or increasing the insecticidal activity of the polypeptide.
A nearest prior art, Varga et al. (Megaphylogeny resolves global patterns of mushroom evolution, 2019, Nat. Ecol. Evol., 3: 668–678) describes a protein comprising at least 95% sequence identity to instant SEQ ID NOs: 1 and 10 (data not shown) obtained from a fungus Dendrothele bispora using genome sequencing (p.7, para 2, line 1-2). Another nearest prior art, Matabaro et al. (Identification, heterologous production and bioactivity of lentinulin A and dendrothelin A, two natural variants of backbone N‑methylated peptide macrocycle omphalotin A, 2021, Scientific Reports, 11:3541) describes pesticidal activity against plant pathogenic nematode (Meloidogyne incognita) by a (borosin) peptide found in the same fungus, Dendrothele bispora (abstract, line 12-15; p.3. Fig 1C). However, that is a separate protein as compared to any of the claimed polypeptides (SEQ ID NOs: 1, 2, 4-8, 10, 12, 15, 21- 25, and 29-34). The nematotoxic polypeptide comprises a “core peptide” of only 12 amino acid long (WVIVTGIVGVIG) (p.3. Fig 1C) that confer the nematotoxicity of the protein. Matabaro et al. teaches that a single specific Valine residue is crucial to nematocidal activity of the peptide (p.7, para 2, line 12-13). A skilled artisan would acknowledge that mutating even a single amino acid can drastically change any one or more function(s) of a protein.
Current status of the art does not provide representative examples to enable a skilled artisan to mutate up to 14 amino acid in any of the claimed sequences (SEQ ID NOs: 1, 2, 4-8, 10, 12, 15, 21- 25, and 29-34) while maintaining and/or increasing pesticidal activity of the protein.
The structure function relationship is even more important for this invention as this protein appears to be a novel protein with specific insecticidal function. It does not have any prior characterization of its domains and sequences in terms of its function(s), unlike many other insecticidal proteins known in the art. The description of the invention does not characterize SEQ ID NO: 1 such that one skilled artisan would know which amino acid residues should not be changed to retain/improve the claimed functions.
Considering the breadth of the claims, lack of representative species of the broad genus claimed, lack of structure function relationship of the broad genus claimed, and unpredictability of the art, the Applicant does not appear to have been in possession of the claimed genus at the time this application was filed.
Scope of Enablement
Claims 6-10 and 14-16 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 proteins comprising 100% sequence identity to instant SEQ ID NOs: 1, 2, 4-8, 10, 12, 15, 21- 25, and 29-34, does not reasonably provide enablement for proteins comprising less than 100% sequence identity to instant SEQ ID NOs: 1, 2, 4-8, 10, 12, 15, 21- 25, and 29-34. 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 use the invention commensurate in scope with these claims.
The Applicant describes identifying a novel polypeptide sequence (SEQ ID NO: 1) comprising intertidal activity (spec, p.33, para 000116, line 1-2) and then created several variants (SEQ ID NO: 2-56) with increased insecticidal activity, altered spectrum of insecticidal activity, increased durability, or increased stability (spec, p.33, para 000116, line 2-4). Different proteins are expressed in either E coli (spec, p. 33, Example 2, line 1-2) or transiently expressed in Nicotiana benthamiana to identify specific insecticidal activity (spec, p. 36, para 000122, line 1-2). The results of insecticidal activity of various proteins (variants of SEQ ID NO: 1) are summarized in Table 1 and Table 2.
Not all the claimed polypeptide sequences (SEQ ID NOs: 1, 2, 4-8, 10, 12, 15, 21- 25, and 29-34) are tested by the Applicant against representative species of all available plant pathogens or pests that would include virus, bacteria, fungi, bacteria, nematodes, mites, ticks etc. besides insect pests. The specification shows in Table 1 that the polypeptide set forth in SEQ ID NO: 23 does not show any pesticidal activity against any plant pathogen or pest when expressed in E coli. Table 2 shows that SEQ ID NOs: 6, 7 and 10 do not show any activity when expressed in a plant leaf. The other sequences (SEQ ID NOs: 12, 15, 21-25 and 29-34) encompassed by the claims are not even tested in a plant tissue. It is also noted in Table 2 that SEQ ID NO: 1 is expressed in a plant leaf assay, using different expression cassettes, which gave different results. It is unclear what the differences are between these cassettes, and how they affect the activity of SEQ ID NO: 1 in the assay. It is unclear whether a particular plant-expressible promoter, other regulatory element(s), or the expressed sequence itself, is/are necessary for pesticidal activity in a plant.
Moreover, the Applicant does not provide any guidance for any skilled artisan to mutate up to 14 amino acids, i.e., 5% of the (about 285) amino acid long polypeptides, anywhere along the entire length of the proteins while retaining or increasing the insecticidal activity of the polypeptide.
Current status of the art does not provide any example to enable a skilled artisan to mutate up to 14 amino acid in any of the claimed sequences (SEQ ID NOs: 1, 2, 4-8, 10, 12, 15, 21- 25, and 29-34) while maintaining and/or increasing pesticidal activity of the protein. The nearest prior art, Varga et al. describes a protein comprising 100% sequence identity to instant SEQ ID NO: 1 (data not shown) obtained from a fungus Dendrothele bispora using genome sequencing (p.7, para 2, line 1-2). Another prior art, Matabaro et al. describes pesticidal activity against plant pathogenic nematode (Meloidogyne incognita) by a (borosin) peptide found in the same fungus, Dendrothele bispora (abstract, line 12-15; p.3. Fig 1C). However, this is a separate protein as compared to any of the claimed polypeptides (SEQ ID NOs: 1, 2, 4-8, 10, 12, 15, 21- 25, and 29-34). The protein comprising a “core peptide” of only 12 amino acid long (WVIVTGIVGVIG) (p.3. Fig 1C) (which is less than 5% of the amino acid long polypeptides as claimed herein) confer the nematotoxicity of the protein. A skilled artisan would acknowledge that mutating even a single amino acid can drastically change any one or more function(s) of a protein. In fact, Matabaro et al. teaches that a specific Valin residue is crucial to the nematocidal activity of the polypeptide (p.7, para 2, line 12-13).
Undue trial and error experimentations would be needed to mutate up to 14 amino acid in any of the claimed sequences (SEQ ID NOs: 1, 2, 4-8, 10, 12, 15, 21- 25, and 29-34) while maintaining and/or increasing pesticidal activity of the protein.
Based on breadth of the claims, lack of any working example, lack of guidance in the instant description or in prior art, the specification at the time of the application filed would not have taught one skilled in the art how to make and use the full scope of the claimed invention without performing undue experiments.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 9 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 9 depends from claim 6 and recites, “The recombinant nucleic acid molecule of claim 6, wherein the polypeptide is any one of SEQ ID NOs: 1, 2, 4-8, 10, 12, 15, 21-25, and 29-34 or a variant thereof having pesticidal activity and at least 95% sequence identity thereto”.
Claim 9 does not further restrict claim 6.
Applicant may cancel the claim(s), amend the claim(s) to place the claim in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Conclusion
No claim is allowed.
It is noted that the SEQ ID NO: 1 is known in the prior art. Varga et al. describes a polynucleotide sequence found in a fungus, Dendrothele bispora, encoding a protein (UniProt Accession No. A0A4S8L0Z3 and GenBank Accession No. THU82046) comprising 100% sequence identity to instant SEQ ID NOs: 1 which is having at least 95% sequence identity to all other claimed sequences including SEQ ID NO: 10. However, the function of the protein, especially in terms of its pesticidal activity, is free of prior art.
Communication
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAY CHATTERJEE whose telephone number is (703)756-1329. The examiner can normally be reached (Mon - Fri) 8.30 am to 5.30 pm..
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J.C.
/Jay Chatterjee/ Examiner, Art Unit 1662
/BRATISLAV STANKOVIC/ Supervisory Patent Examiner, Art Units 1661 & 1662
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