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 .
New 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.
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 1 and 4-6 are rejected under 35 U.S.C. 103 as being unpatentable over Ryan et al., (WO 2000/063347 A1, Oct. 26, 2000) (cited by Examiner Form 892 09/10/2025) (hereinafter Ryan) in view of Donata (Functional Characterization Of Tomato Prosystemin And Prosystemin Regions: Novel Tools For Plant Defense, December 28, 2018) (cited by Applicant on IDS 05/10/2023) (hereinafter Donata).
Ryan discloses methods of augmenting plant defenses, in particular the generation of active oxygen species (AOS), against predator attack (i.e., biotic stress) that include the steps of (a) introducing a nucleic acid molecule (i.e., sequence) that encodes a protein selected from the group consisting of systemin, prosystemin and polygalacturonase into plant cells (Abstract). Systemin is an 18 amino acid polypeptide, isolated from the leaves of tomato plants, that induces the synthesis of numerous wound-inducible proteins (i.e., abiotic stress). Systemin is synthesized as part of a larger, 200 amino acid precursor protein called prosystemin. Systemin induces an active oxygen species response, and that plants that overexpress prosystemin have an augmented active oxygen species response (page 2, lines 24-29). Plant cells are eukaryotic host cells to which DNA is introduced in the form of a vector containing an inserted piece of DNA (i.e., expression vector) (page 6, lines 29-34). Sequence variants of proteins may be used to attain desired enhanced or reduced enzymatic activity (page 5, lines 20-22). Insertional protein variants are those with one or more amino acids inserted immediately adjacent to an amino acid at a particular position in the native protein molecule connected to either the -carboxy or α-amino functional group of the amino acid (page 6, lines 1-4). Representative examples of nucleic acid molecules that are useful in the practice of the invention encode a prosystemin protein molecule that has at least 70% amino acid sequence identity, with the tomato prosystemin protein sequence set forth in SEQ ID NO:2. Sequence identity is determined by aligning the tomato prosystemin protein sequence set forth in SEQ ID NO:2 with another sequence and introducing gaps, if necessary, to achieve the maximum percent identity. No weight is given to the number or length of gaps introduced, if necessary, to achieve the maximum percent identity (page 7, line 31 to page 8 line 3). Sequence variants, produced by deletions of the proteins useful in the practice of the invention can also be used in the methods of the invention (page 9 line 37 – page 10 line 1). Oligonucleotide-directed mutagenesis may be employed to conveniently prepare the deletion and insertion variants of proteins useful in the practice of the invention (page 11, lines 34-37). Generally, oligonucleotides of at least 25 nucleotides in length are used to insert, delete or substitute two or more nucleotides in the nucleic acid molecules encoding proteins useful in the practice of the invention. An optimal oligonucleotide will have 12 to 15 perfectly matched nucleotides on either side of the nucleotides coding for the mutation (page 12, lines 4-8). Seq ID NO:8 comprises 16 amino acids (i.e., wherein the isolated peptide has a length ranging from 9 to 120 amino acids) (Sequence Listing, page 5) and may be used in methods of the invention (Claim 3). Seq ID NO:2 is as follows:
PNG
media_image1.png
183
577
media_image1.png
Greyscale
PNG
media_image2.png
486
653
media_image2.png
Greyscale
(Sequence Listing, bottom of page 2 – top of page 3). As shown in SEQ ID NO:2 of Ryan above, SEQ ID NO 2 of the instant claims is identical to amino acids 1-120 of the amino acid sequence of Ryan.
Ryan differs from the instant claims insofar as not disclosing wherein the isolated peptide is derived from the N- terminal region of prosystemin, and is free of the C-terminal 18-amino acid systemin peptide, and wherein the isolated peptide has essentially an intrinsically disordered configuration.
However, Donata teaches that prosystemin is an Intrinsically Disordered Protein (IDP) and may exert its multifaceted biological activity as a consequence of its intrinsic disorder suggesting new interesting insights on the role prosystemin in plant response against biotic and, possibly, abiotic stressors (page 69, fourth paragraph). Evidences suggest that prosystemin N-terminal region, deprived of Systemin, could have a role in plant defense responses. This hypothesis was verified by producing the recombinant fragments corresponding to these regions. Four purified fragments were produced including Fragment I and III which cover the N-terminal region of the prosystemin protein. The biophysical and the biochemical characterization of these regions showed that all the recombinant fragments are disordered in agreement with what previously shown for the whole precursor (bottom of page 69 – top of page 70). Fragments I and III were considered the most interesting ones as they do not include systemin (i.e., free of the C-terminal 18-amino acid systemin peptide) and therefore represent novel peptides likely associated with plant defense responses (page 70, second paragraph).
As discussed above, Ryan discloses the tomato prosystemin protein sequence set forth in SEQ ID NO:2, sequence variants, produced by deletions of the proteins useful in the practice of the invention can also be used in the methods of the invention, and teaches that sequence variants of proteins may be used to attain desired enhanced or reduced enzymatic activity. Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to have used Fragment I and III of (i.e., peptides) which cover the N-terminal region of the prosystemin protein, do not include systemin, and are intrinsically disordered, in the methods disclosed by Ryan since they are known and effective prosystemin sequence variants associated with plant defense responses as taught by Donata.
Regarding the limitation of claim 1 reciting an isolated peptide consisting of an amino acid sequence selected from the group consisting of SEQ ID NOs. 1, 2, 3-9, 23-26, as discussed above, Ryan teaches that no weight is given to the length of gaps introduced to achieve the maximum percent identity and that sequence variants, produced by deletions of the proteins useful in the practice of the invention can also be used in the methods of the invention. Thus, the isolated peptide consisting of the amino acid sequence of SEQ ID NO:2 of the instant claims has a 100% sequence identity to the amino acid sequence SEQ ID NO:2 of Ryan.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Ryan et al., (WO 2000/063347 A1, Oct. 26, 2000) (cited by Examiner Form 892 09/10/2025) (hereinafter Ryan) and Donata (Functional Characterization Of Tomato Prosystemin And Prosystemin Regions: Novel Tools For Plant Defense, December 28, 2018) (cited by Applicant on IDS 05/10/2023) (hereinafter Donata) in view of Ree et al., (Spotlight On Protein N-Terminal Acetylation, July 27, 2018) (hereinafter Ree).
The teachings of Ryan and Donata are discussed above. Ryan and Donata do not teach wherein the amino-terminal end is modified by acetylation and/or the carboxy-terminal end is modified by amidation.
However, Ree teaches N-terminal acetylation (Nt-acetylation) is a widespread protein modification among eukaryotes and prokaryotes alike. By appending an acetyl group to the N-terminal amino group, the charge, hydrophobicity, and size of the N-terminus is altered in an irreversible manner. This alteration has implications for the lifespan, folding characteristics and binding properties of the acetylated protein (Abstract). Nt-acetylation has many functions in the cell. A) In some cases, Nt-acetylation targets proteins for polyubiquitination and proteasomal degradation, and in other cases, it protects against such degradation. B) Nt-acetylation is required for the proper folding of some proteins. C) Protein–protein interactions (PPIs) in protein complex formation are in some cases mediated or augmented by Nt-acetylation. D) Nt-acetylation serves to target some proteins for membranes, either through PPIs with an integral membrane protein or through direct interactions with membrane lipids (page 5, Fig. 3 Functions of N-terminal acetylation).
Ryan teaches that sequence variants of proteins may be used to attain desired enhanced or reduced enzymatic activity (page 5, lines 20-21). Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to modify the amino-terminal end of the protein of Ryan in view of Donata by acetylation to attain the desired enzymatic activity because Nt-acetylation targets proteins for proteasomal degradation, and in other cases, it protects against such degradation, as taught by Ree. One would have a reasonable expectation of success since Ryan teaches that insertional protein variants having one or more amino acids inserted immediately adjacent to an amino acid at a particular position in the native protein molecule connected to the α-amino functional group of the amino acid are suitable sequence variants.
Claims 8-9 and 11-12 are rejected under 35 U.S.C. 103 as being unpatentable over Ryan et al., (WO 2000/063347 A1, Oct. 26, 2000) (cited by Examiner Form 892 09/10/2025) (hereinafter Ryan) and Donata (Functional Characterization Of Tomato Prosystemin And Prosystemin Regions: Novel Tools For Plant Defense, December 28, 2018) (cited by Applicant on IDS 05/10/2023) (hereinafter Donata) in view of Sawant et al., (US 2021/0188726 A1, filed July 15, 2019) (hereinafter Sawant).
The teachings of Ryan and Donato are discussed above. Ryan and Donata do not teach a composition comprising at least one peptide according to claim 1, and at least one adjuvant, stabilizer and/or preservative.
However, Sawant discloses an agricultural composition, such as water dispersible granules, or a liquid suspension composition for soil application comprising at least one amino acid, their polymers, salts or derivatives or mixtures thereof, elemental sulphur, and at least one structuring agent. The agricultural composition further includes plant growth promoters (Abstract). The amino acids may be peptides ([0037]) and are present in a concentration range of from 0.1% to 70% by weight of the total composition ([0039]). The liquid suspension may be an aqueous suspension formulation (i.e., a water-based liquid composition) ([0032]) comprising wetting agents (i.e., an adjuvant) ([0069]). The agricultural composition in the form of water dispersible granules is made by various techniques such as freeze drying (i.e., lyophilized form) ([0127]). The composition can also be useful to improve plant vigor and mitigate plant stresses like saline stress, drought stress, heat stress, cold stress, salt stress, micro nutrient stress and any other biotic and abiotic stresses of crop plant ([0136]). Improved plant vigor includes improved defense mechanism of the plant such as induced tolerance against fungi, bacteria, viruses and/or insects ([0137]). Sawant teaches that amino acids are very useful to improve the production and the quality of the crop as they are building blocks of proteins, which exert manifold functions in plant metabolism, and as metabolites and precursors wherein they are involved with plant defense, stress management ([0005]).
Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use. See MPEP 2144.07. Sawant discloses wherein the composition comprises peptides. Accordingly, it would have been obvious to one of ordinary skill in the art to have the protein sequence (i.e., peptide) of Ryan in view of Donata into the composition of Sawant since it is a known and effective protein sequence (i.e., peptide) useful for augmenting plant defenses, as taught by Ryan.
Regarding the limitation of claim 9 reciting wherein the at least one peptide is present in a concentration ranging from 0.01 picomolar (pM) to 100 pM, as discussed above, Sawant teaches that amino acids may be peptides and are present in a concentration range of from 0.1% to 70% by weight of the total composition. Further, amino acids are very useful to improve the production and the quality of the crop as they are building blocks of proteins, which exert manifold functions in plant metabolism, and as metabolites and precursors wherein they are involved with plant defense, stress management. Accordingly, one of ordinary skill in the art would have been capable of arriving at a peptide concentration ranging from 0.01 picomolar (pM) to 100 pM though routine experimentation based on the desired function of the amino acid, as taught by Sawant. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. See MPEP 2144.05(II)(A).
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Ryan et al., (WO 2000/063347 A1, Oct. 26, 2000) (cited by Examiner Form 892 09/10/2025) (hereinafter Ryan), Donata (Functional Characterization Of Tomato Prosystemin And Prosystemin Regions: Novel Tools For Plant Defense, December 28, 2018) (cited by Applicant on IDS 05/10/2023) (hereinafter Donata), and Sawant et al., (US 2021/0188726 A1, filed July 15, 2019) (hereinafter Sawant) further in view of de Souza et al., (Plant growth-promoting bacteria as inoculants in agricultural soils, May 22, 2015) (hereinafter de Souza).
As discussed above, Ryan, Donata, and Sawant make obvious the limitations of claim 8 but do not teach wherein the composition further comprises a microorganism selected from the group consisting of mycorrhizal fungi, saprophytic fungi, plant growth promoting bacteria, Bacillus thuringiensis spores, and any combination thereof.
However, de Souza teaches that plant growth-promoting bacteria (PGPB) are bacteria that can enhance plant growth and protect plants from disease and abiotic stresses through a wide variety of mechanisms. Bacterial inoculants can contribute to increase agronomic efficiency by reducing production costs and environmental pollution, once the use of chemical fertilizers can be reduced or eliminated if the inoculants are efficient (abstract). The introduction of beneficial bacteria in the soil tends to be less aggressive and cause less impact to the environment than chemical fertilization, which makes it a sustainable agronomic practice and a way of reducing the production costs (page 412, Conclusions).
As discussed above, Sawant discloses agricultural compositions for soil application comprising at least one amino acid and plant growth promoters. It would have been prima facie obvious to one of ordinary skill in the art to formulate the composition of Sawant to comprise a plant growth promoting bacteria since plant growth-promoting bacteria are bacteria that can enhance plant growth and protect plants from disease and abiotic stresses and their introduction to soil tends to be less aggressive and cause less impact to the environment than chemical fertilization, as taught by de Souza.
Response to Applicant’s Arguments
Applicant’s arguments have been considered but are moot because new rejections necessitated by Applicant’s amendments have been made.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Samantha J Knight whose telephone number is (571)270-3760. The examiner can normally be reached Monday - Friday 8:30 am to 5:00 pm ET.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ali Soroush can be reached at (571)272-9925. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/S.J.K./Examiner, Art Unit 1614
/ALI SOROUSH/Supervisory Patent Examiner, Art Unit 1614