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 .
Claim Status
Claims 1-26 pending and being examined.
The claim amendments by the Applicant especially the removal of most of the previous species (SEQ ID NOs: 4, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33 and 35) including the one (SEQ ID NO: 13) on which previous Office action (dated 8/8/2025) was issued, and retaining SEQ ID NO: 1 as the only species to be examined, give rise to new issues and necessitated new prior art references and/or new grounds of rejections, as discussed below.
The Applicant is reminded that the Requirement for Restriction Office action, dated 5/5/2025, was based on the initial claims (submitted to the Office on 9/12/2023). The claims did not comprise SEQ ID NO: 1. The Applicant amended the relevant claims (dated 7/7/2025) including claim 1 and removed all the SEQ ID NOs previously present in those claims and added new set of SEQ ID NOs comprising SEQ ID NO: 1, and then elected SEQ ID NO: 1. However, the Examiner rejoined SEQ ID NO: 13 for subsequent examination of the claims.
All previous objections and rejections not set forth below have been withdrawn in view of Applicant’s amendments to the claims.
Claim Rejections - 35 USC § 112(a)
Scope of Enablement
Claims 1-26 remain 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 a polypeptide having 100% sequence identity to SEQ ID NO: 1, does not reasonably provide enablement for all the myriad variants of polypeptides having at least 95% sequence identity to SEQ ID NO: 1 while the modified polypeptide, when expressed, delay flowering time, increase shoot dry weight, and/or increase tolerance to drought. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Claims 1-26 are broadly drawn to a plant cell, plant seed, or plant comprising at least one heterologous promotor operably linked to a nucleic acid segment encoding a RFS polypeptide that has at least 95% amino acid sequence identity to SEQ ID NO: 1, while overexpression of the polypeptide delays flowering time, increases shoot dry weight, and/or increases tolerance to drought.
The Applicant describes a polypeptide comprising SEQ ID NO: 1, encoded by the polynucleotide SEQ ID NO: 2 from A. thaliana (page 11-12, para 0032-0034).
The Applicant does not describe any representative working example of a polypeptide having less than 100% identity to SEQ ID NO: 1. The Applicant describes the newly identified plant-specific gene family (Regulator of Flowering and Stress family, RFS) comprising a single N-terminal transmembrane helix and a conserved but uncharacterized domain in the RFS polypeptide (Spec, page 10-11, para 0030). However, the Applicant does not describe if any of the domain(s) in the RFS polypeptide is related to and/or confer any of the claimed biological function(s). The Applicant does not provide any guidance that would enable any skilled artisan to mutate up to 5% or up to 9 amino acids in 191 amino acid long SEQ ID NO: 1, while gaining or maintaining one or more function(s) of the RFS polypeptide comprising delayed flowering, increased shoot dry weight, and/or drought tolerance.
Nearest prior art, Cheng et al. (Araport11: a complete reannotation of the Arabidopsis thaliana reference genome, 2017, The Plant Journal, 89, 789–804), GenBank Accession No. Q9M250 (published in 2006) and Alexandrov et al. (US 2018/0223303 Al, published in 2018; SEQ ID NOs: 405171 and 3218584) describe a polypeptide sequence comprising 100% identity to SEQ ID NO: 1. However, none of them describe any of the biological functions including flowering time, shoot dry weight, and/or tolerance to drought being related to the polypeptide.
Current status of the art also does not provide any guidance to enable any skilled artesian to mutate up to 9 amino acids along the entire length of the polypeptide comprising SEQ ID NO: 1 while maintaining one or more of the said function(s).
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Using the BLAST® search of instant SEQ ID NO: 1 in the GenBank reveals only one known (zinc finger CCHC-type) but seemingly unrelated protein while almost all proteins are uncharacterized or hypothetical proteins, see above.
The Applicant does not provide any guidance on how to use a protein having 95% identity to instant SEQ ID NO: 1, so far the use of the protein and/or the plant expressing the protein is concerned and in context of the present invention.
Undue trial and error experimentations would be needed for any skilled artisan to mutate up to 5% of SEQ ID NO: 1 while the mutated polypeptide gaining or retaining one or more of said function(s) relevant to this invention.
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 use the full scope of the claimed invention without performing undue experiments.
Written Description
Claims 13-17 and 24-26 remain 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 inventors, at the time the application was filed, had possession of the claimed invention.
Claim 13-17 and 24-26 are broadly drawn to a plant cell, plant seed, or plant , or a method of generating such a plant that overexpresses a RFS polypeptide that has at least 95% amino acid sequence identity to SEQ ID NO: 1 using a heterologous promoter conferring one or more gain-of function trait(s) comprising delayed flowering, increased shoor dry weight, and/or abiotic stress comprising drought tolerance.
The Applicant describes a polypeptide comprising SEQ ID NO: 1, encoded by the polynucleotide SEQ ID NO: 2 from A. thaliana (page 11-12, para 0032-0034).
However, the Applicant does not describe any representative number of species having less than 100% identity to SEQ ID NO: 1, while claiming the broad genus.
Mutating up to 5% amino acid residues in 191 amino acid long SEQ ID NO: 1 would allow mutating up to 9 amino acids. The Applicant describes the newly identified plant-specific RFS gene family comprising a single N-terminal transmembrane helix and a conserved but uncharacterized domain in the RFS polypeptide (Spec, page 10-11, para 0030). However, the Applicant does not describe if any of the domain(s) is related to and/or confer any of the claimed biological function(s).
The Applicant also does not describe any structure function relationship to enable a skilled artisan to mutate up to 9 amino acid residues in SEQ ID NO: 1 while achieving and/or retaining one or more of the function(s) comprising delayed flowering, increased shoot dry weight, and/or increased abiotic stress including drought tolerance.
Nearest prior art, Cheng et al., GenBank Accession No. Q9M250 (published in 2006), and Alexandrov et al. describe a polypeptide sequence comprising 100% identity to SEQ ID NO: 1. However, none of the references describes any of the biological functions including flowering time, shoot dry weight, and/or tolerance to any abiotic stress including drought in relation to the polypeptide.
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, the Applicant does not appear to have been in possession of the claimed genus at the time this application was filed.
Response to Applicant’s arguments:
The Applicant argues that, “In view of the disclosure of amino acid sequences, including SEQ ID NO: 1, those skilled in the art could readily envision all of the amino acid sequences that are 95% identical to any of the disclosed amino acid sequences…. Such manipulations of nucleic acids, amino acids and testing are routine to those of ordinary skill in the art.” (bridging paragraph between last para of page 7 and first para of page 8 in Applicant’s response). The Applicant continues to argue that, “the art and the specification provide assay procedures for determining the activity of such molecules. Such manipulations of nucleic acids/amino acids and testing are routine to those of ordinary skill in the art and do not require undue experimentation (response, page 8, para 2, line 1-3).
The Examiner disagrees. The rejections under 112(a), (both “scope of enablement” and “written description”) boil down to “at least 95% amino acid sequence identity” to SEQ ID NO: 1, which an ordinarily skilled or a skilled artisan can make but cannot use commensurate with the nature of invention considering the level of predictability in the art, amount of directions (for “scope of enablement”) or structure-function relationship (for “written description”) provided by the Applicant, working examples provided needed to “possess” and/or the quantity of experimentation to use the invention based on the content of the disclosure. See MPEP See MPEP § 2164 and 2163.
Based on the knowledge in the art, a skilled artisan can make a protein having at least 95% sequence identity to instant SEQ ID NO: 1. However, the “scope of enablement” rejection, as described above, is not based on making the protein, but using the invention commensurate with the nature of invention (i.e., achieving delayed flowering, increased shoot dry weight, and/or increased abiotic stress including drought tolerance) considering the level of predictability in the art.
An ordinarily skilled artisan would acknowledge that a change of even one amino acid along the entire length of a polypeptide can drastically alter the function of the mutated polypeptide. The function of the mutated protein becomes even more unpredictable if we consider compensatory mutations (CMs) that can counter balance the effects of a mutation (Banerjee et al., Compensatory Mutations Occur Within the Electrostatic Interaction Range of Deleterious Mutations in Protein Structure, 2015, J Mol Evol, 80:10–12; abstract).
The Applicant does not provide representative number of species having less than 100% identity to SEQ ID NO: 1, while claiming the broad genus. The Applicant also does not provide any guidance or structure-function relationship to enable a skilled artisan to mutate up to 9 amino acid residues along the entire length of SEQ ID NO: 1 or mutate a totally unrelated protein to achieve 95% identity (to SEQ ID NO: 1) while achieving and/or retaining one or more of the function(s) comprising delayed flowering, increased shoot dry weight, and/or increased abiotic stress including drought tolerance.
The Applicant is reminded that an invention described solely in terms of a method of making and/or its function may lack written descriptive support where there is no described or art-recognized correlation between the disclosed function and the structure(s), which include(s) polynucleotide and/or polypeptide sequences and/or specific domains therein, responsible for the function. See MPEP § 2163.
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.
Claims 2, 13-17 and 21 remain 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.
The term “strong” in claims 2 and 21 is a relative term which renders the claim indefinite. The term “strong” 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.
The Applicant describes, “a strong promoter provides for a high level of gene expression, whereas a weak promoter provides for a very low level of gene expression.” (page 36, para 00126, line 1-3). Thus, the attempted definition is based on other relative terms. However, the term “strong” is not defined in the specification to differentiate with obverse “weak” promoters. It is not clear as to what extent an ordinarily skilled artisan or the Examiner would interpret the term “strong” or how high the level of expression of a promoter needs to be to qualify as “strong”, as per the broadest reasonable interpretation (BRI).
Claims 13-17, dependent from claim 2, also inherit the indefiniteness.
Response to Applicant’s arguments:
The Applicant arguses that, “Strong promoters, including strong promoters in plants, are a term well known in molecular biology that identifies promoters that drive a high level of gene expression” (page 9, para 2, line 1-2) and cites 35SCaMV as an example of “strong” promoter (Page 9, para 3, line 3-6)
It is known in the art that some commonly used promoters like 35S CaMV may be considered “strong” for expression in certain plants and/or certain plant cells/tissues, but its expression can be “weak” in certain other plants including certain mosses like Physcomitrella patens and under specific growth condition(s), e.g., under darkness1. Similarly, 35SCaMVpromoter does not express at all in certain cell/tissue types and considered “weak” for other cell/tissue type in a plant2. Claims 2, 13-17 and 21 comprises all plants, all cell and/or tissue types in a plant while claims 2-3 recites inducible and tissue-specific promoters where expression level of a promoter can vary significantly.
Claim Rejections - 35 USC § 102
Claims 1-12 and 17-26 remain rejected under 35 U.S.C. 102(a)(1) as anticipated by Alexandrov et al. (US 2018/0223303 Al, published in 2018), in evidence of Koropatkin et al. (How glycan metabolism shapes the human gut microbiota, 2012, Nat. Rev. Microbiol., 10: 323–335).
Claim 1 is drawn to a plant cell, plant seed, or plant comprising at least one heterologous promotor operably linked to a nucleic acid segment encoding a RFS polypeptide that has at least 95% amino acid sequence identity to SEQ ID NO: 1, wherein the promoter and nucleic acid segment is endogenously expressed or encoded in an expression system.
Alexandrov et al. describes a plant (A. thaliana) comprising a polypeptide sequence (SEQ ID NO: 405171) having 100% sequence identity to instant SEQ ID NO: 1, as shown below.
RESULT 1
US-15-706-418-405171
Filing date in PALM: 2017-09-15
Sequence 405171, US/15706418
GENERAL INFORMATION
APPLICANT: ALEXANDROV, Nickolai
APPLICANT: APUYA, Nestor
APPLICANT: BROVER, Vyacheslav
APPLICANT: CHEN, Xianfeng
APPLICANT: DUMAS, Jean-Baptiste
APPLICANT: FANG, Yiwen
APPLICANT: FELDMANN, Kenneth
APPLICANT: MASCIA, Peter
APPLICANT: OKAMURO, Jack
APPLICANT: PENNELL, Roger
APPLICANT: SCHNEEBERGER, Richard
APPLICANT: SUBRAMANIAN,Gopalakrishnan
APPLICANT: TROUKHAN, Maxim
APPLICANT: ZHANG, Liansheng
TITLE OF INVENTION: SEQUENCE DETERMINED DNA FRAGMENTS AND CORRESPONDING POLYPEPTIDES
TITLE OF INVENTION: ENCODED THEREBY
FILE REFERENCE: 2750-1571PUS2
CURRENT APPLICATION NUMBER: US/15/706,418
CURRENT FILING DATE: 2018-02-02
SEQ ID NO 405171
LENGTH: 191
TYPE: PRT
ORGANISM: Arabidopsis thaliana
FEATURE:
NAME/KEY: misc_feature
LOCATION: (1)..(191)
OTHER INFORMATION: Ceres Seq. ID no. 405171
Query Match 100.0%; Score 1036; Length 191; Best Local Similarity 100.0%;
Matches 191; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MATLDSPLEVLAFDYVNFVFNNLWTWIAVVTAAVSFWRIRATTTTTTSGGGRDNGLIDES 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MATLDSPLEVLAFDYVNFVFNNLWTWIAVVTAAVSFWRIRATTTTTTSGGGRDNGLIDES 60
Qy 61 FLEPPKPQATKAALLMETKPPRVKVTETEDWSLLLCKDGVTKGKLTVYYEEEIDGEREED 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 FLEPPKPQATKAALLMETKPPRVKVTETEDWSLLLCKDGVTKGKLTVYYEEEIDGEREED 120
Qy 121 DGETTAVKYGGGESGEWWERWERVVKMRNGDEGWYRYVDLTVINGNVVRLWDANRVRNGG 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 DGETTAVKYGGGESGEWWERWERVVKMRNGDEGWYRYVDLTVINGNVVRLWDANRVRNGG 180
Qy 181 WVSVQRKECYG 191
|||||||||||
Db 181 WVSVQRKECYG 191
However, Alexandrov et al. does not explicitly teach a RFS polypeptide. However, SEQ ID NO: 405171 is having the same structure of instant SEQ ID NO: 1 and originated in the same plant species, Arabidopsis (A. thaliana). It is inherent that SEQ ID NO: 405171, as taught by Alexandrov et al., is the same polypeptide of instant SEQ ID NO: 1 and would be having the same functions. Alexandrov et al. describes developing transgenic plants via various methods including Agrobacterium-mediated transformation, electroporation, microinjection, particle bombardment (page 221, para 2277) using recombinant DNA construct (abstract) operably linked to a promoter that is functional in a plant (page 4, para 0097, last 2 lines). Alexandrov et al. also describes heterologous promoters (page 8, para 0192).
Regarding claims 2 and 21, Alexandrov et al. describes inducible promoters (page 207, para 2005, line 12; page 220, para 2261, last line; page 220, para 2267, line 6-7).
Regarding claim 3 and 22, Alexandrov et al. describes tissue specific promoters (page 219, para 2261, line 5).
Regarding claim 4, Alexandrov et al. describes a plant comprising a transgene encoding a RFS polypeptide comprising SEQ ID NO: 1, as described above. A transgenic plant developed via agrobacterium-mediated transformation or by bombardment using microparticles coated with a recombinant DNA inherently would integrate the transgene in a non-native location in the host genome.
Regarding claims 5 and 23, Alexandrov et al. describes CaMV35S promoter (page 221, para 2283, line 31-32).
Regarding claims 6, it is well-known that plant-virus-derived (heterologous) CaMV 35S promoter generally increases endogenous expression of a gene under its control relative to the expression of the gene under its own endogenous or native promoter. Thus, the RFS gene being expressed under the control of 35S CaMV promoter, as described by Alexandrov et al., would increases endogenous expression of the RFS gene relative to the expression of an RFS gene without the heterologous promotor. An ordinarily skilled artisan can also replace the endogenous promoter of the endogenous RFS gene with the heterologous 35SCaMV promoter by using a well-known standard technique of CRISPR-Cas, which would satisfy all the claim limitations of claim 6.
Regarding claims 7-9, Alexandrov et al. describes agricultural crops including corn, soybean, soybean, wheat and rice (page 2, para 0032, last 2 lines).
Regarding claim 10, Alexandrov et al. describes sorghum (page 221, para 2280, 2nd last line).
Regarding claim 11, Alexandrov et al. describes sugar beet (page 228, Table 3).
Regarding claim 12, Alexandrov et al. describes cotton (page 228, Table 3).
Regarding claim 17, Alexandrov et al. describes several drought responsive genes (page 4, para 0074) and development of new genotypes including transgenic plants with increased drought tolerance (page 81, last line; page 138, para 1593; page 139, table “stress response”).
Regarding claim 18, Alexandrov et al. describes a method (Abstract, line 5-7) comprising growing a plant and/or a plant seed comprising a heterologous promotor operably linked to a nucleic acid segment encoding a polypeptide (SEQ ID NO: 405171) that has 100% sequence identity to instant SEQ ID NO: 1, as described above. Alexandrov et al. also describes gene constructs and vector construction (page 208, para 2046). “Vector” and/or “vector construction” reads on to an “expression system”, as recited in claim 18 in last line. Alexandrov et al. also teaches regeneration of whole (matured transgenic) plants from transformed plant cells (page 221, para 2279, line 1-2).
As described above, Alexandrov et al. does not explicitly teach a RFS polypeptide. However, SEQ ID NO: 405171 is having the same structure of instant SEQ ID NO: 1. Thus, it is inherent that SEQ ID NO: 405171, as taught by Alexandrov et al., is the same polypeptide as instant SEQ ID NO: 1, and inherently would be having all its function(s).
Regarding claim 19, Alexandrov et al. describes genes that modulate plant biomass (page 37, para 0660, line 7-12). Any ordinarily skilled artisan would be motivated and would know harvesting biomass including seeds from the transgenic plants having increased biomass especially the seeds (grains) in crops where the grains/seeds are of economic importance.
Regarding claim 20, Alexandrov et al. describes generation of transgenic plants with enhanced yield including biomass either directly or via increasing tolerance/resistance against various biotic and/or abiotic stresses (page 32, para 0569, line 5-7). It describes yield (including
biomass (such as fresh and dry weight during any time in plant life, including maturation and senescence), root/tuber yield (such as number, size, weight, harvest index, content and composition, (i.e. amino acid, jasmonate, oil, protein and starch), number of flowers, seed yield, number, size, weight, harvest index, content and composition ( e.g. amino acid, jasmonate, oil, protein and starch), and fruit yield (such as number, size, weight, harvest index, post harvest quality, content and composition, ( e.g. amino acid, jasmonate, oil, protein and starch) (page 33, para 0609, line 10-20). Starch is a glycan consists of glucose monomers (or monosaccharides) (Koropatkin et al., How glycan metabolism shapes the human gut microbiota, 2012, Nat. Rev. Microbiol., 10(5): 323–335; page 22, Focus Box 1, line 1). Isolating commercially important starch and other carbohydrates including oligosaccharides is a known and routine process in the art3
Regarding claims 24-26, Alexandrov et al. describes exposing the plants to abiotic stresses (page 145, para 1640, line 7-8) including various environmental stresses such as drought (page 23, para 0388, line 3-6).
Response to Applicant’s arguments:
The Applicant argues that, “Since the basis of the rejection (under U.S.C. 102) of each of claims 1-12 and 17-26 in view of the Wu reference is the alleged anticipation of SEQ ID NO: 13, and this sequence has been removed from the claims (claim amendments), the Wu reference fails to anticipate the claims” (page 11, last para, last 3 lines).
The Applicant is reminded that the amendments give rise to new issues and necessitated new prior art references including Alexandrov et al., and new grounds of rejections under U.S.C. 102, as discussed above.
Conclusion
No claim is allowed.
However, claims 13-16 are free of prior art.
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.
Communication
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Jay Chatterjee
Patent Examiner
Art Unit 1662
/Jay Chatterjee/Examiner, Art Unit 1662
/BRATISLAV STANKOVIC/Supervisory Patent Examiner, Art Units 1661 & 1662
1 Saidi et al. (The CaMV 35S promoter has a weak expression activity in dark grown tissues of moss Physcomitrella patens, 2009, Plant Signaling & Behavior 4:5, 457-459; Abstract).
2 Sunilkumar et al. (Developmental and tissue-specific expression of CaMV 35S promoter in cotton as revealed by GFP, 2002, Plant Molecular Biology, 50: 463–474; abstract).
3 Cano et al. (Production of Oligosaccharides from Agrofood Wastes, 2020, Fermentation, 6:31) provides the evidence that isolating commercially important starch and other carbohydrates including oligosaccharides is a known and routine process (Abstract and entire article).