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 of Group I comprising claims 1-3, 5-6 and 10-12 in the reply filed on 3/19/2016 is acknowledged. The Applicant also elects SEQ ID NO: 123 and 124 in claim 3.
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)).
Claim Status
Claims 1-3, 5-6, 10-17, 21-22 and 24-28 are pending.
Claims 13-17, 21-22 and 24-28 are not being examined as being part of non-elected Groups.
Claims 1-3, 5-6 and 10-12 are being examined.
Specification
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.
The Applicant mentions https://phytozome.jgi.doe.gov (spec, page 65, para 5-6). It is suggested to delete the other browser-executable hyperlink.
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 1-3, 5-6 and 10-12 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 1 recites, “a method of increasing tolerance to water and/or nutrient deficiency in a plant, comprising: modifying expression or activity of AtExo970, or a homolog or ortholog thereof”.
The Applicant does not define the terms “homolog” and “ortholog”. The commonly used definition of “homolog” (or “homologues” as per British English) are defined based on its evolution and not based on either functional or sequence similarity. “Homologous genes become separated in evolution in two different ways: separation of two populations with the ancestral gene into two species or gene duplication of the ancestral gene within a lineage”, as described by the document published by National Library of Medicine, NIH (as part of a workshop held on August 3, 2023). It is accepted in the art that all homologs are also orthologs but not all orthologs are homologs.
The Applicant describes identification of AtExo970 (AtExo970 cDNA- SEQ ID NO: 123; AtExo970 protein- SEQ ID NO: 124); homologs from other crop and vegetable species using publicly available whole genome sequences at https://phytozome.jgi.doe.gov (spec, page 65, para 5-6). Homologs of AtExo970 from 6 species such as canola, soybean, corn, wheat, Brachypodium and rice have been identified and used as examples in the invention. (page 65, para 6, line 3-6).
Several Arabidopsis genome sequencing and/or genome annotation projects have identified the gene and the protein having 100% sequence identity to the entire length protein recited as “AtExo970”. One such example (GenBank accession number: ACF16171) identifies the protein as “C2H2 Zinc finger” protein and “RNA exonuclease 4”. The name AtExo970 appears in this application for the first time. It is fair to say that the current status of the art does not describe any AtExo970 gene or protein.
There are exonucleases in the prior art having at least 50% seq identity to Seq 124. A quick search in the Uniprot database shows that the protein (AtExo970) is classified as “RNA exonuclease 4” and there are 235 “homologues” and/or “orthologs” that have at least 50% sequence identity to SEQ ID NO: 124 (AtExo970) (data not shown). The Applicant describes such nucleases from 6 species- canola, soybean, corn, wheat, Brachypodium, and rice; and the lowest sequence identity (between AtExo970 and GmExo740) being 50%.
The Applicant does not describe any structure and function relationship (to become a homolog and/or ortholog) for the AtExo970. The Applicant does not describe any structure and function relationship of AtExo970 or any of its holomolgs/orthologs in relation to its exonuclease activity and/or the function of increasing tolerance to water and/or nutrient deficiency.
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 1-3, 5-6 and 10-12 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 overexpressing of the AtExo970 or a homolog or ortholog thereof, does not reasonably provide enablement for all other types of modification of gene expression. 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.
Claim 1 recites “… modifying expression or activity of AtExo97…”.
The Applicant describes screening about 27,000 Arabidopsis T-DNA activation tag lines and 3 mutant lines to identify plants in which silique (pod) length is not dramatically affected by the (drought) stress (spec, page 20, para 5, line 10-13). Subsequent analysis with a mutant line (d200) with water stress condition help identifying the At3g27970 gene, which is annotated as “zinc ion binding exonuclease family protein possibly involved in ribosomal RNA (rRNA) processing” and named AtExo970 in the instant invention (P. 22, para 4, line 1-3). Thus, the terminology, “AtExo970” is not used in the art before.
Constitutive overexpression of AtExo970 improves drought tolerance and productivity (p. 25, para 7). All the “homologs” (based on sequence homology/identity) of AtExo970 from different plant species, as described, are cloned in plant expression vector(s) under the control of a constitutive promoter (e.g. 35S CaMV) and used to transform different plants (page 28-45). A loss of function mutation is achieved for AtExo970 via CRISPR based gene editing (page 54, last para). However, there is no result in terms of its phenotype/trait especially in relation to water and/or nutrient deficiency is described by the Applicant.
The Applicant does not provide any guidance regarding how myriad different modifications of expression or activity of AtExo970 (mutations) other than overexpression and specific mutation(s) (d200, which are also overexpression lines due to T-DNA activation tag), described herein, would affect the tolerance to water and/or nutrient deficiency in a plant. Current status of the art also does not provide any guidance regarding how different modifications of expression or activity of AtExo970 other than overexpression would affect the tolerance to water and/or nutrient deficiency in a plant.
Undue trial and error experimentations would be needed to determine if modifications of expression or activity of AtExo970 other than overexpression would increases tolerance to water and/or nutrient deficiency in a plant. And there can be myriad of such modifications of expression or activity including specific indel and/or substitution mutation(s) of the specific gene, AtExo970. The situation gets more complicated once we include similar modifications of a homolog or ortholog of AtExo970.
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.
Claims 5-6 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 replacing the native promoter or the native gene (which includes the native promoter) encoding said AtExo970, homolog or ortholog thereof, does not reasonably provide enablement for all other mutations of the native promoter or the gene encoding said AtExo970, homolog or ortholog thereof, or replacing a portion of said promoter or the said gene that does not overexpress the native protein AtExo970 or the homolog or ortholog thereof. 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 screening about 27,000 Arabidopsis T-DNA activation tag lines and thee d200 mutant lines to identify plants in which silique (pod) length is not dramatically affected by the stress (spec, page 20, para 5, line 10-13). Subsequent analysis with a mutant line (d200) with water stress condition help identifying the At3g27970 gene, which is annotated as “zinc ion binding exonuclease family protein possibly involved in ribosomal RNA (rRNA) processing” and named AtExo970 in the instant invention (P. 22, para 4, line 1-3). Constitutive overexpression of AtExo970 improves drought tolerance and productivity (p. 25, para 7).
Constitutive overexpression of AtExo970 improves drought tolerance and productivity (p. 25, para 7). All the “homologs” (based on sequence homology/identity) of AtExo970 from different plant species, as described, are cloned in plant expression vector(s) under the control of a constitutive promoter (e.g. 35S CaMV) and used to transform different plants (page 28-45). A loss of function mutation is achieved for AtExo970 via CRISPR based gene editing (page 54, last para). However, there is no result in terms of its phenotype/trait especially in relation to water and/or nutrient deficiency is described by the Applicant.
The Applicant does not provide any guidance regarding how myriad different mutations including replacing “portion of”of the native promoter(s) AtExo970 gene, its homolog or ortholog ; or “portion of the gene” itself, other than overexpression, would affect tolerance to water and/or nutrient deficiency in a plant. Current status of the art also does not provide any guidance regarding how different modifications of the native promoter(s) and/or the gene itself of AtExo970 gene or its homolog or ortholog, other than overexpression, would affect the tolerance to water and/or nutrient deficiency in a plant.
Undue trial and error experimentations would be needed to determine if modifications of the native promoter AtExo970 gene or its homolog or ortholog, other than overexpression, increase tolerance to water and/or nutrient deficiency in a plant. There can be myriad of such modifications including specific indel and/or substitution mutation(s) in the native promoters(s) alone. The situation gets more challenging once we include more modifications in terms of “replacing a portion of (the) said gene”. Even overexpression of the gene may not result in increasing tolerance to water and/or nutrient deficiency if the mutated gene encodes functionally a very different protein with altered activity or no functional activity at all, in terms of tolerance to water and/or nutrient deficiency.
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 § 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 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Davies et al. (US 7,763,771 B2, published on 27 July 2010) in view of Osuna et al. (Temporal responses of transcripts, enzyme activities and metabolites after adding sucrose to carbon-deprived Arabidopsis seedlings, 2007, The Plant Journal, 49, 463–491) and in evidence of Li et al. (Precise gene replacement in plants through CRISPR/Cas genome editing technology: current status and future perspectives, 2020, aBIOTECH, 1:58–73)
Claim 1 is drawn to a method of increasing tolerance to water and/or nutrient deficiency in a plant by modifying expression or activity of AtExo970, or a homolog or ortholog thereof.
Davis et al. describes a method to improve oil quantity (IOQ) or improved meal quality (IMQ) by modifying the expression of specific polynucleotide sequences (abstract). Ectopic expression of an IMQ polypeptide in several transgenic plants of different species result in an altered oil content, an altered protein content, and/or an altered fiber content in the transgenic plant (column 4, line 13-21). Davis et al. describes regenerating and growing the modified (transgenic) plants (column 26, line 34-36), as recited in claim 2. Davis et al. also describes cloning the transgene under the control of strong constitutive CsVMV and seed specific PRU promoters (column 43, line 39-41), as recited in claim 5. Davis et al. teaches an herbicide resistance selectable marker gene in the expression vector pSK1015 (column 26, line 33-36), as recited in claim 12.
One of the IMQ polypeptides (IMQ75.2 and SEQ ID NO: 102) is encoded by the Arabidopsis gene At5g40310 (GenBank Accession No. NM_001344320) encoding an exonuclease (Table 2, column 35-36). Arabidopsis gene At5g40310 has 82.5% sequence identity to instant SEQ ID NO: 123 (data not shown) and 83.6% sequence identity to instant SEQ ID NO: 124 (as recited in claim 3), as shown below.
RESULT 1
US-11-940-284-102
Sequence 102, US/11940284
Patent No. 7763771
GENERAL INFORMATION
APPLICANT: Agrigenetics, Inc.
APPLICANT: Davies, John
APPLICANT: Ng, Hein Tsoeng (Medard)
APPLICANT: D. Ry, Wagner
TITLE OF INVENTION: GENERATION OF PLANTS WITH ALTERED PROTEIN, FIBER, OR OIL CONTENT
FILE REFERENCE: 7896-72540-41
CURRENT APPLICATION NUMBER: US/11/940,284
CURRENT FILING DATE: 2007-11-14
PRIOR APPLICATION NUMBER: US 60/866,060
PRIOR FILING DATE: 2006-11-15
NUMBER OF SEQ ID NOS: 122
SEQ ID NO 102
LENGTH: 348
TYPE: PRT
ORGANISM: Arabidopsis thaliana
Best Local Similarity 83.6%; Query Match 84.3%; Score 1609; Length 348;
Matches 290; Conservative 28; Mismatches 29; Indels 0; Gaps 0;
Qy 11 ETLRNKCAACYRQFNKLEHLVEHMKISYHSGHEPTCGVCKKHCRSFESLREHLIGPLPKQ 70
:| |||| ||||||| |||||||:||||| ||||||:| ||||||:|||||||||||||
Db 2 DTCRNKCGGCYRQFNKKEHLVEHMRISYHSVHEPTCGICNKHCRSFDSLREHLIGPLPKQ 61
Qy 71 ECKNIFSLRGCRFCMTILESPNSRRIHQERCQFSSVNSGLTTRMAALGLRDKAMIDYTSS 130
|||||||:||||||:|||||||:||||||||| |:| ||| ||||||||: : ||||||
Db 62 ECKNIFSIRGCRFCLTILESPNARRIHQERCQLSNVTSGLMIRMAALGLRNNSTIDYTSS 121
Qy 131 RSPRVVALSCKMVGGGSDGSLDLCARVCITDESDNVIFHTYVKPSMAVTSYRYETTGIRP 190
|||||||||||||||||||||||||||||||||:||:|||||||:: ||:|||| |||||
Db 122 RSPRVVALSCKMVGGGSDGSLDLCARVCITDESENVVFHTYVKPTIPVTNYRYEMTGIRP 181
Qy 191 ENLRDAMPLKQVQRKIQEFLCNGEPMWKIRPRGGKARILVGHGLDHDLDRLQLEYPSSMI 250
||||||| || |||:|||||||||||||||| ||||||||||||: || ||||| ||||
Db 182 ENLRDAMRLKHAQRKVQEFLCNGEPMWKIRPRNGKARILVGHGLDNHLDSLQLEYSSSMI 241
Qy 251 RDTAKYPPLMKTSKLSNSLKYLTQAYLGYDVHFGIQDPYEDCVATMRLYTRMRYQKHKIE 310
||||:||||||:||||||||||||||||||:| ||||||||||||||||||||||||: |
Db 242 RDTAEYPPLMKSSKLSNSLKYLTQAYLGYDIHVGIQDPYEDCVATMRLYTRMRYQKHRAE 301
Qy 311 AYPLAADAQNRSNQVAWRQSEAERMSPDEMLSISRSDYYCWCLDSLA 357
|||||:| || :| ||||:| |||||:|:| :||||||||||||:|
Db 302 AYPLASDTQNHNNFAAWRQNELERMSPEELLDLSRSDYYCWCLDSVA 348
Davis et al. also describes that rice (Oryza sativa, Japonica cultivar) has ortholog of the At5g400310 (column 41-42).
The Applicant does not define “homolog” or “ortholog”. However, the Applicant describes proteins having at least 50% sequence identity to instant SEQ ID NO: 124 as homolog and/or ortholog. Thus, SEQ ID NO: 102 of Davis et al. would read on to “homolog” and/or “ortholog” of the exonuclease AtEXO970 set forth by instant SEQ ID NO: 124.
However, Davis et al. do not describe increased tolerance to water and/or nutrient deficiency.
Osuna et al. describes that over 50 transcription regulators (TRs) undergo at least fivefold change of expression after carbon (source) starvation and/or sucrose readdition (Table 1) (page 468, left column, para 1, line 1-3). One of the TRs is At5g40310 (page 469, Table 1).
It would have been obvious to an ordinarily skilled artisan to modify the expression of Arabidopsis gene At5g40310, as described by Davis et al.
The artisan would have been motivated to modify the expression of Arabidopsis gene At5g40310 to improve oil and/or meal quality in a plant. Modification of the expression of the At5g40310 gene or its ortholog in rice (as described by Davis et al.) would also enable the plant to cope with nutrient (carbon) deficiency (as recited in claims 1-2), as described by Osuna et al. Selection of transgenic plants for specific trait(s) including increased tolerance to water and/or nutrient deficiency is well-known and standard process in the art.
Regarding claims 5-6 and 10-11; It would have been obvious to one with ordinary skill in the art to substitute the native promoter with strong constitutive promoters including CsVMV or PRU promoters, as described by Davis et al. (column 43, line 39-41) using well-known and the standard process of CRISPR-Cas based gene editing. Using/expressing a suitable Cas endonuclease, designing suitable gRNA to replace specific target sequence including the native promoter (Li et al., p. 61-62, Table 1; page 62, right column, para 1, line 15-19) of the specific gene is also a known and standard practice in the art.
Prior Art Not Applied
It is prudent to mention here that the instant invention describes using Arabidopsis d200 mutant line (spec, page 20, para 5, line 10-13) to identify the AtExo970 gene. It implies that the mutation(s) is/are in the D200 gene (or its homolog/ortholog) in Arabidopsis. There is a prior art (Akilan et al., Evaluation of osmotic stress tolerance in transgenic Arabidopsis plants expressing Solanum tuberosum D200 gene, 2019, Journal of Plant Interactions, 14:79–86), which is not used or mentioned in any rejection discussed above, describing a D200 gene in potato. Overexpression of the potato D200 gene in Arabidopsis is shown to increase tolerance to osmotic stress (reads on to “water deficiency”) tolerance (Abstract).
Conclusion
No claim is allowed.
Contact Detail
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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/Jay Chatterjee/Examiner, Art Unit 1662
/BRATISLAV STANKOVIC/Supervisory Patent Examiner, Art Units 1661 & 1662
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