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 without traverse of Group I: Claims 1-9 in the reply filed on July 20, 2026 is acknowledged. This Restriction/Election Requirement is made FINAL.
Claims 1-20 are pending. Claims 10-20 are withdrawn as a result from the Restriction/Election Requirement. Claims 1-9 are examined on their merit herein.
Claim Rejections - 35 USC § 112
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, 4, 5, and 9 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.
Claim 2 is rejected as being indefinite for the recitation of (the absence of) “substantial reduction” in grain yield. The term “substantial” is a relative term which renders the claim indefinite. The term “substantial” 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 Specification has not provided any definition regarding the degree or criteria for assessing if a reduction in grain yield is “substantial” or not. The metes and bounds are therefore not clear.
Similarly, claim 4 is rejected as being indefinite for the recitation of “substantially tolerant” to lodging. The Specification has not provided any definition regarding the degree or criteria for assessing if a reduction in the context of lodging is “substantial” or not. Thus, the term “substantial” is a relative term which renders the claim indefinite. The term “substantial” 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 metes and bounds are therefore not clear.
Similarly, claim 5 is rejected as being indefinite for the recitation of “substantially similar or slightly reduced” in the context of ear height. The Specification has not provided any definition regarding the degree or criteria for assessing if a reduction in the context of lodging is “substantial” or not. In particular, the working examples provided in the Specification—presumably representing embodiments encompassed by the claims, indicates a “change” in ear height of “24% and up”. It is unclear whether a “24%” change is considered “substantially similar or slightly reduced”. It is further unclear whether “24% and up”—which appear to encompass 30%, 50%, or more, should be considered as “substantially similar or slightly reduced” . Thus, the terms “substantially similar or slightly reduced” are relative terms which renders the claim indefinite. The terms are 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 metes and bounds are therefore not clear.
Claim 9 is similarly rejected as being indefinite for the recitation of deletion of a “substantial portion” of the polynucleotide encoding the D8 polypeptide. It is unclear which degree of a deletion is considered a substantial portion. The metes and bounds are therefore not clear.
Claim 9 is rejected as being indefinite for the recitation of a polypeptide comprising an amino acid sequence that is at least 95% identical to a sequence selected from the group consisting of SEQ ID NOS: 73-75 SEQ ID NOS: 73-75 are nucleotide sequences. It is unclear how an amino acid sequence is determined to have 95% identity to a nucleotide sequence.
Claim 9 recites the limitation "the Dwarf8 (D8) genomic locus " in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 112
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.
Lack of Written Description
Claims 1-9 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 Federal Circuit has clarified the application of the written description requirement. The court stated that a written description of an invention "requires a precise definition, such as by structure, formula, [or] chemical name, of the claimed subject matter sufficient to distinguish it from other materials". University of California v. Eli Lilly and Co., 119 F.3d 1559, 1568; 43 USPQ2d 1398, 1406 (Fed. Cir. 1997). The court also concluded that "naming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not description of that material". Id. Further, the court held that to adequately describe a claimed genus, Patent Owner must describe a representative number of the species of the claimed genus, and that one of skill in the art should be able to "visualize or recognize the identity of the members of the genus". Id.
The claims are broad in scope in the following aspects:
Claims 1-4 and 6 encompass any modification of any genomic locus involved in gibberellic acid (GA) signaling, in any plant species;
Claim 5 encompasses any modification of any genomic locus involved in gibberellic acid (GA) signaling, in a maize plant;
Claims 7-8 encompass any modification of a Dwarf8 (D8) genomic locus in a maize plant;
Claim 9 is drawn to the method comprising introducing an “edit” at the maize D8 locus, such that the edit results in one or more of the following:
reduced expression of a polynucleotide encoding the D8 polypeptide;
reduced activity of the D8 polypeptide;
generation of one or more alternative spliced transcripts of a polynucleotide encoding the D8 polypeptide;
deletion of one or more domains of the D8 polypeptide;
frameshift mutation in one or more exons of a polynucleotide encoding the D8 polypeptide;
deletion of a substantial portion of the polynucleotide encoding the D8 polypeptide or deletion of the polynucleotide encoding the D8 polypeptide;
repression of an enhancer motif present within a regulatory region encoding the D8 polypeptide; and
modification of one or more nucleotides or deletion of a regulatory element operably linked to the expression of the polynucleotide encoding the D8 polypeptide, wherein the regulatory element is present within a promoter, intron, 3’UTR, terminator or a combination thereof.
Claims require the broad genus of introduced genetic modification to result in reducing plant height; and/or a specific range of reduced plant height; and/or with no reduction in grain yield and/or no reduction in ear height.
Firstly, the broad nature of any GA signaling elements in any plants should be discussed. Even the key regulator—the so called DELLA proteins—are diverse among different plant species. For example, the DELLA protein is redundant in Arabidopsis as it encodes 5 different DELLA proteins: GAI, RGA, RGL1, 2, and 3, whereas rice encodes only one DELLA protein, SLR1. Consequently, loss-of-function mutation of DELLA protein is not found in Arabidopsis. Further, even the GID1-GA-DELLA system is conserved in vascular plants but not in nonvascular plants. However, such a conserved GID1-GA-DELLA system downstream of the DELLA protein is more complicated. The DELLA proteins have 2 func- tions. One functions as a repressor by interacting with the TF and disrupts it to contact the cis element of the GA-induced gene. Meanwhile, the other functions as a co-activator by interact- ing with TFs and activating GA feedback-regulated genes. (Ueguchi-Tanaka, Miyako. "Gibberellin metabolism and signaling." Bioscience, Biotechnology, and Biochemistry 87.10 (2023): 1093-1101).
Gazara also teaches that important aspects regarding the origin of GA perception system remain to be elucidated. While the lycophyte Se. moellendorffii and the bryophyte Physcomitrella patens have some of the key components of the canonical GA perception machinery, several lines of evidence indicate the absence of a functional GA signaling pathway is the bryophytes, such as: (1) Ph. patens GID1 and DELLA do not interact; (2) Ph. patens GID1 does not interact with GA; (3) DELLA-deficient Ph. patens strains do not exhibit derepressed growth like that observed in DELLA-deficient angiosperms; (4) Ph. patens DELLA does not suppress GA response in rice, although it can repress growth in Ar. thaliana. (Gazara, R.K., Moharana, K.C., Bellieny-Rabelo, D. et al. Expansion and diversification of the gibberellin receptor GIBBERELLIN INSENSITIVE DWARF1 (GID1) family in land plants. Plant Mol Biol 97, 435–449 (2018).)
Secondly, the claims encompass a broad range of genetic modifications that could have diverse and distinct effects. For example, Ueguchi-Tanaka teaches the rice slender 1 mutant (slr1) which shows the opposite phenotype of Ara-bidopsis gai, that is, GA overdose phenotype, such as slender stature and pale green leaves, even in the presence of a GA synthetic inhibitor, even though SLR1 encodes a rice DELLA protein.
In contrast to the broad scopes encompassed by the claims, the Specification has only inadequately described one species from the broad genus of structures, as shown below:
The Specification has mentioned methods of targeted gene editing using CRISPR-Cas system, with the gRNAs “CR2” and “CR3” (Table 2) complementary to the nucleotide sequence of maize D8 gene (encoding the polypeptide sequence of SEQ ID NO: 76). As known in the prior art, and stated in the Specification (e.g., p. 40, lines 13-18; and elsewhere regarding the CRISPR technique, and references therein), the guided cleavage of the target gene (D8) by CR2-CR3 gRNAs would be followed by either homologous result in any number of deletion, insertion, substitution, or addition, or combinations thereof, anywhere in the region corresponding to CR2 and CR3, and in its vicinity.
The Specification has provided the following support for genetic modifications modify the DELLA domain of the encoded polypeptide in the genomic locus corresponding to a target region represented by SEO ID NOs: 62 and 63:
In Table 2: “Deletion from position 408 to 963 of the gene (556 bp of gene); removes N-terminal DELLA domain (by dual gRNA)”. As discussed above, this “deletion of 556 bp” results in a deletion of 37 nucleotides in the promoter region adjacent to the protein coding sequence, the first 37 codons (amino acids) before DELLA domain, the DELLA domain, AND 70 amino acids after DELLA domain. It should be noted that Applicant has not provided any phenotypic description of this variant (“D556” hereinafter).
In Table 3: Applicant listed a number of edited variants, including the “recreated” DELLA domain mutants taught in the prior art. However, it should be noted that Applicant has not provided any evidence or phenotypic description of the variants in Table 3, especially 1) whether there is height reduction and if so, how much and 2) whether the plants are free of detrimental pleiotropic effects.
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In Table 6: Applicant listed 5 genome edited maize variants: GV2.9, GV2.15, etc., having “genetic modifications modify the DELLA domain of the encoded polypeptide in the genomic locus corresponding to a target region represented by SEO ID NOs: 62 and 63”. Note that only variant “GV2.15” showed a reduction of plant height (of 50% in the heterozygous mutant).
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Regarding the disclosure, it should be noted that Applicant has only described (in the Specification above, one variant “GV2.15” that resulted in height reduction (a reduction by 50% in the hemizygote, and a reduction by 62% in the homozygote) (see Table 6 above). As seen above in Table 6, 4 out 5 of other genome-edited variants with deletions and insertions in the locus defined by CR2/CR3 (SEQ ID NO: 62/63) had no reduction in plant height.
Furthermore, the ear height of the edited plants with plant height reduction (e.g., variant “GV2.15” above) also has significant reduction (by 64%) in the homozygous mutant plant.
Due to the nature of DNA codons, a deletion or insertion of any number of nucleotide that is no divisible by 3, in the coding sequence, would potentially cause a frameshift and have profound effect of the encoded protein. The instant Table 6 lists (see captured Table 6 above), after modification guided by CR2/CR3, insertions and deletions of 1, 2, 23, and 7 nucleotides at presumably 5’ side of the D8 coding sequence (it should be noted that Applicant has NEVER disclosed exactly where those deletions are). Since 1, 2, 23, and 7 are all not divisible by 3, it is possible these deletion would cause frameshift and abolishing the DELLA domain in the encoded protein. Yet, these were shown to have NO height reduction.
The only modified plant has height reduction (by 50%) is a variant called “GV2.15” (although it is unclear how a 50% reduction would be representative of the claimed “reduced up to 30%). It is also noted the Specification, as it stands, does not provide any description of the exact modification in variant “GV2.15”, other than the rather cryptic description “-579 bp with 44 insertion”—without describing which 579 nucleotides were deleted and where, and what, were the 44 nucleotide insertions. There is no description anywhere in the instant disclosure regarding what nucleotides were deleted and what nucleotides were inserted and how the insertion/deletion would impact the encoded protein, especially regarding DELLA domain.
Even assuming the 579nt deletion spans from the 5’UTR region (where CR2/SEQ ID NO: 62 resides) to CR3/SEQ ID NO: 63 (approximately codon 181), it is not clear what the 44nt insertion is and how would that 44bp insertion would alter the edited D8 gene, in term of transcription control, or translation. There is no description or evidence showing what the edited D8 variant actually encode, or what the encoded protein resembles, in term of structure and function.
Therefore:
Applicant has not provided adequate description of the broad genus of “genomic locus comprises a polynucleotide involved in gibberellic acid signaling” in any plant species, and the broad genus of “nucleotide modifications” that would result in reduced plant height.
Applicant has not provided adequate description of the broad genus of “genomic locus comprises a polynucleotide involved in gibberellic acid signaling” in maize, and the broad genus of “nucleotide modifications” that would result in reduced plant height.
Applicant has not provided adequate description of the broad genus of “nucleotide modifications” of a broad genus of maize genomic locus comprises a polynucleotide having 95% identity to SEQ ID Nos: 73-75, and the broad genus of that would result in reduced plant height.
Applicant has not provided adequate description of the broad genus of “nucleotide modifications” of maize D8 locus that would result in reduced plant height by specifically 5% to 30%, with no reduction in grain yield, and/or with the ear height as measured to the maize plant height substantially similar or slightly reduced.
The prior art teaches a number of maize D8 mutant alleles with mutations (“modifications”) in or around DELLA domain. For example: Winkler (Planta 193.3 (1994): 341-348.) teaches dominant dwarfs DS-1, D8-2023, D8-81127, D8-1452, D8-Mpl and D8-1591, with various degree of plant height reduction (~20% reduction in D8-Mpl, to ~80% reduction in D8-1; see Fig. 3, captured in the withdrawn rejection under 103);
Peng (Peng, Jinrong, et al. "‘Green revolution’genes encode mutant gibberellin response modulators." nature 400.6741 (1999): 256-261.) teaches the identification of the mutations in maize D8 alleles such as D8-1 and D8-mpl. Peng teaches that “three maize mutant proteins (D8-1, D8-2023 and D8-Mpl), like Arabidopsis gai, lack regions of the peptide sequence. D8-1 and D8-2023 are, like gai, in-frame deletion mutations. In D8-1, D55 is replaced by a glycine, and 56-VAQK-59 are missing. This segment is very close to that deleted in gai, and falls within the highly conserved region I (Fig. 3a). D8-2023 lacks 87-LATDTVHYNPSD-98 from within the highly conserved region II (Fig. 3a). The D8-Mpl mutation is a 330-base pair (bp) deletion that extends from the 59 untranslated sequence through the presumed (normal) start ATG codon and ends at V84.” (p. 259, and Fig. 3; partially captured here for convenience).
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Peng teaches the amino acid sequence of maize D8 (Fig. 2), which is the same as the instant SEQ ID NO: 76.
Thus, Winkler together with Peng, teach at least three D8 mutants with “genetic modifications” in the DELLA domain.
Winkler teaches that “each dominant D8 allele were observed to have four pleiotropic effects in addition to dwarfing: (i) increased tillering, (ii) delayed flowering, (iii) andromonoecious phenotype, and (iv) reduced number of anthers exserted.” (p. 345, right, para. 2).
Thus, prior art has demonstrated D8 mutations in the DELLA domain while result in reduced plant height, also cause negative pleiotropic effects to the maize plants.
The state of the art—as well as the instant Specification, demonstrates that even the gRNA-guided gene editing based on the CRISPR system, would result in a broad range of mutations even when guided by a specific gRNA. For example, Yang, et al. (CRISPR/Cas9-mediated genome editing efficiently creates specific mutations at multiple loci using one sgRNA in Brassica napus. Sci Rep 7, 7489 (2017)) teaches genome editing of Brassica DELLA protein BnaRGAs which are orthologs of Arabidopsis REPRESSOR OF GA1-3 (RGA) gene, master repressors in gibberellic signaling, using two sgRNAs for each gene. Yang teaches a range of mutations resulted from the targeted modification, “deletions, insertions, substitutions, and combined mutations (i.e., more than one mutation type in one allele) (Fig. 1A and B). The mutations ranged from short nucleotide changes (≤3-bp) such as one nucleotide insertions (Fig. 1B), to deletions from one bp to hundreds of bp (p.4, para. 3; and Fig. 1). Furthermore, Yang teaches that plants exhibit a range of phenotypes from various degree of dwarfism to increased plant height (Fig. 3).
Moreover, both the Specification and the prior art testify for the complex interaction between D8 mutations and the genetic background, in the manifest of the phenotypes. For example, the Specification at p. 66, lines 17-19, states that “In a few cases, edited variants appear to have taller stature, illustrating the wide range of genetic variations and their impact on plant architecture phenotype.” As the Specification demonstrated in Table 6, 4 out 5 gene edited maize plant variants using gRNAs CR2 and CR3, have no height reduction. Since those D8-edition are all mediated by gRNAs CR2 and CR3, AND all resulted in genetic modifications (e.g., 23-nt deletion in “GV3.15” with a plant height of 104%; see Table 6), the Specification has not described 1) the nature of genetic modifications in the variants, and 2) how the “genetic variations” that would determine phenotypes regarding both the plant height and negative pleiotropic effects.
In summary, the Specification has not provided the structure-function relationship required for the broadly claimed genetic modification to result in the required phenotype. Especially, the Specification has not described which structural element(s) in the DELLA domain should be modified—and how—to result in a D8-modified maize plant with the required degree of height reduction without negative pleiotropic effects on crop yield. While the CRISPR-Cas system guided by CR2-CR3 would result in any modification of the DELLA domain, the Specification has not provided any description which kind of modification, and where, to arrive at the required phenotypes.
The nature of “GV2.15” mutation sequence is critical to understand the structure-function relationship between the broad genus of modification to the specific phenotypes as claimed.
As discussed above, the Specification listed the “GV2.15” mutant as having “-579 bp with 44 bp insertion” without specifying which 579 bp of maize D8 were deleted and what 44bp are inserted. More importantly, it is not described what the resulted protein or translated polypeptide has, structurally. This is important because the different resulted polypeptide may have unpredictable and dramatic differences not only in the degree of dwarfism, but also in other (negative) traits. For example, Thomas (Thomas, Stephen G. "Novel Rht-1 dwarfing genes: tools for wheat breeding and dissecting the function of DELLA proteins." Journal of Experimental Botany 68.3 (2017): 354-358) teaches that: “The agronomically important Rht-B1b and Rht-D1b semi-dwarfing alleles contain mutations that introduce premature stop codons in the region of these genes encoding the N-terminal GID1–GA binding domain (Peng et al., 1999; Pearce et al., 2011; Box 1). It is believed that the effect of these mutations is to produce an N-terminally truncated protein which cannot be bound by the GID1–GA receptor, therefore resisting GA-mediated degradation and acting to constitutively repress GA-responsive growth and development. The severe dwarfing allele, Rht-B1c, also contains a lesion in the N-terminal coding region, which is predicted to have the same effect on perturbing GA signalling. However, in this case, the increased stability of RHT-B1C is due to a 30-amino acid insertion within the GID1–GA binding domain (Pearce et al., 2011; Wu et al.,2011). Although conclusive biochemical evidence is lacking, the current consensus of opinion regarding the milder GA-insensitive phenotype observed in Rht-B1b and Rht-D1b compared to Rht-B1c is due to a lower level of accumulation of the N-terminally truncated proteins produced by a process of translational reinitiation (Peng et al., 1999).” (p.355, top, emphasis added). In the instantce case, since the mutant “GV2.15” is allegedly different from other edited mutants in the disclosure, and from the numerous D8 alleles in the prior art, it is critical to understand the structural basis for this difference, in order to provide written description support for a broad genus of D8 modifications that would meet the claimed scope.
Therefore, Applicants have not adequately described the structural features that are required to be retained by members of the broad genus as to establish a structure-function relationship, or the structural features required to distinguish members of the claimed genus from other chemical structures.
The analysis now turns to the second element of the court’s decision in Eli Lilly; namely, the description of a representative number of species. For example, the DELLA domain of maize D8 (SEQ ID NO: 76) has 74 amino acids. Even a single substitution at any of the 74 positions to any of the other 19 amino acids, would result in a genus of mutants encompassing at least 1974 (~4 x 1094) possible combinations of single substitution mutants in a small domain of a specific protein. The claims are even broader in scope as encompassing any type and size of modifications in anywhere of the coding, non-coding, and regulatory sequences of the D8 locus, or any genes directedly or indirectly related to GA signaling in any plant species.
Given the virtually infinite structural variable associated with these embodiments, the claims read on an extremely broad and highly diverse structures. Thus, in view of the analysis presented above, a skilled artisan would appreciate that the claims are directed to extremely broad and highly diverge genus of protein variants that are required to have the specific function required by the claims.
Given the large size and structural diversity associated with the claimed genus, Applicant’s disclosure is not representative of the claimed genus as a whole.
Thus, based on the analysis above, Applicant has not met either of the two elements of the written description requirement as set forth in the court's decision in Eli Lilly. As a result, it is not clear that Applicant was in possession of the claimed genus at the time this application was filed.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-4 and 6 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Allen (US20180051295A1, effective filing date Aug. 17, 2017; Published Feb. 22, 2018).
Claim 1 is drawn to a method of reducing plant height, the method comprising introducing one or more nucleotide modifications through a targeted site-directed modification at a genomic locus of a plant, wherein
(a) the genomic locus comprises a polynucleotide involved in gibberellic acid signaling, and
(b) wherein the plant height is reduced compared to a control plant not comprising the one or more introduced genetic modifications.
Claim interpretation:
The term “polynucleotide involved in gibberellic acid signaling” is interpreted as any polynucleotide involved in gibberellic acid signaling in any manner. Support for this interpretation comes from at least the following:
Dependent claim 7 recites the genomic locus encoding a “polynucleotide involved in gibberellic acid signaling” as encompassing “an endogenous polynucleotide encoding a polypeptide that is involved in plant height”;
Specification at [0015], the “gibberellic acid biosynthesis or signaling pathway” encompasses br2 (Item f). Since BR2 is a P-glycoprotein (PGP1) auxin transporter, the Specification appears to broadly include the crosstalk between GA and auxin as part of the signaling; and
The state of the art teaches that part of GA signaling includes the feedback regulation of GA biosynthesis. For example, see Ueguchi-Tanaka which teaches “Gibberellin represses the gene expression of some GA- positive regulators, such as biosynthetic enzymes GA20 oxidase and GA 3oxidase, GID1, and SCARECROW-like3 (CL3), through the GA signaling pathway, which is a well-known feedback repression.” (p. 1097, right, para. 3; Ueguchi-Tanaka, Bioscience, Biotechnology, and Biochemistry 87.10 (2023): 1093-1101).
Allen discloses genome editing at or near the GA20 oxidase_3 gene with an RNA-guided endonuclease, ([0161]), and the RNA-guided endonuclease may be targeted to an upstream or downstream sequence, such as a promoter and/or enhancer sequence, or an intron, 5′UTR, and/or 3′UTR sequence of a GA20 oxidase_3 or GA20 oxidase_5 gene to mutate one or more promoter and/or regulatory sequences of the gene and affect or reduce its level of expression ([0162]); with expression of one or both of these genes e reduced or eliminated through genome editing it would produce corn plants having the beneficial short height traits without off-types in the ear, and that expression directly in reproductive ear tissues also does not give rise to reproductive off-types, it is proposed that one or both of these gene loci may be edited to knock-down or knock-out their expression to produce similar effects in corn plants.([0186]); wherein modified corn plants are provided that have a plant height that is at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, ….. less than the height of a wild-type or control plant (1.e., reduced by at least 5%, 10%, …… 30%) ([0204]; and modified corn plants may comprise a reduced lodging frequency ([0210]).
Therefore, under the BRI, claims 1-4 and 6 are anticipated by the prior art.
Claims 1 and 6 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Feng, et al., Efficient genome editing in plants using a CRISPR/Cas system. Cell Res 23, 1229–1232 (2013).
Feng discloses CRISPR/Cas based disruption of GIBBERELLIC ACID INSENSITIVE (GAI) gene in Arabidopsis thaliana (a method of introducing site-directed modification of a genomic locus encoding a gene involved in GA signaling in a plant) (p. 1229, right column; and Fig.1) whereby more than a quarter of the T1 plants for GAI also showed a dwarf phenotype (Figure 1D), and wherein The designed target for GAI is located in the DELLA domain (Supplementary information, Figure S1C).
Therefore, claims 1 and 6 are anticipated by the prior art.
Claims 1, 3, and 6 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lu et al., Precise Editing of a Target Base in the Rice Genome Using a Modified CRISPR/Cas9 System. Molecular Plant, 2016; 10, 523-525.
Lu discloses targeted editing of rice SLR1 which encodes a DELLA protein, wherein the C/T substitution lines gave an obvious semi-dwarf phenotype (Figure 1H, line 07).
Based on Fig. 1H, mutant line SLR#07 has a plant height of approximated 5/8 the control plant, therefore meets the instantly claimed “plant height is reduced by about 30% compared to the control plant.” Given that the Specification has not defined what “about 30%” is, the reduction of approximately 37.5% is interpreted as being “about 30%”.
Therefore, claims 1, 3, and 6 are anticipated by the prior art.
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Claims 1 and 6 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Li et al., (2016) Reassessment of the Four Yield-related Genes Gn1a, DEP1, GS3, and IPA1 in Rice Using a CRISPR/Cas9 System. Front. Plant Sci. 7:377; with evidence from He et al. "IPA1 negatively regulates early rice seedling development by interfering with starch metabolism via the GA and WRKY pathways." International Journal of Molecular Sciences 22.12 (2021): 6605.
Li discloses using the CRISPR/Cas9 system to mutate the IPA1 (Os08g0509600) gene of rice (Abstract); Where base deletions cause a frameshift in the protein (as in ipa1-5) which may completely inactivate the protein, the mutant plants have a dwarf phenotype with an increased number of tillers (Figures 4 F,G). Although Li is silent regarding gibberellic acid signaling, He teaches that IPA1 negatively regulates early rice seedling development by interfering with starch metabolism via the GA and WRKY pathways (Title). Thus under BRI, IPA1 is a gene “involved in gibberellic acid signaling” and “an endogenous polynucleotide encoding a polypeptide that is involved in plant height.”
Therefore, claims 1 and 6 are anticipated by the prior art.
Claim Rejections - 35 USC § 103
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, and 6-9 are rejected under 35 U.S.C. 103 as being unpatentable over Winkler (Planta 193.3 (1994): 341-348.) in view of Peng (Nature vol. 400,6741 (1999): 256-61), Feng (Cell research 23.10 (2013): 1229-1232.), and Char (Plant biotechnology journal 15.2 (2017): 257-268. published August 2016)
Winkler teaches maize plants having mutations in the maize D8 (Dwarf-8) gene, e.g., D8-mpl (D8-Miniplant), as well as other alleles such as D8-2023, D8-1452, D8-81127, and D8-1591, wherein the D8 alleles were introgressed into “WT inbreds B73, Mo17 and in some cases W23”, which are “lines from standard corn-belt germplasm.” (p. 342, “Materials and methods”).
As such, the maize lines B73, Mo17, are “elite” lines according to the instant disclosure, since they are firstly, widely used for commercial agricultural production (as “standard corn-belt germplasm”), and secondly, widely used for maize breeding. For example, Stonaker (US 8134047 B2) stated “Elite inbred lines (B73,……” (Col. 21, line 41) were used.
Therefore, Winkler teaches elite maize plants modified (via breeding methods) to have a genetic modification in the D8 gene.
Winkler teaches that, when the elite maize plants are introgressed with the D8 genetic modification, such as B73, Mo17, the maize plants have a reduction of plant height, of various degrees, depending on the D8 alleles. For example, D8-mpl NIL lines in B73 or Mo17 background have a relative plant height of 76% to 78% compared with control (p. 345, left column; and Fig. 3 which is captured here for convenience of reference). This translates to a reduction of plant height by 22-24% caused by the D8-mpl allele. Thus, Winkler teaches an elite maize plant with a genetic modification in D8 gene having its plant height “reduced to up to 30%” (D8-1) or “reduced by up to 30%” (D8-mpl).
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596
574
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(Captured from Winkler; lines added to indicate the relative plant heights of B73 and Mo17 lines carrying D8-mpl allele).
Winkler does not directly teach the sequence of the D8 gene or its encoded D8 polypeptide, or the targeted site-directed modification in the D8 locus.
Peng teaches the identification of the mutations in maize D8 alleles such as D8-1 and D8-mpl. Peng teaches that “three maize mutant proteins (D8-1, D8-2023 and D8-Mpl), like Arabidopsis gai, lack regions of the peptide sequence. D8-1 and D8-2023 are, like gai, in-frame deletion mutations. In D8-1, D55 is replaced by a glycine, and 56-VAQK-59 are missing. This segment is very close to that deleted in gai, and falls within the highly conserved region I (Fig. 3a). D8-2023 lacks 87-LATDTVHYNPSD-98 from within the highly conserved region II (Fig. 3a). The D8-Mpl mutation is a 330-base pair (bp) deletion that extends from the 59 untranslated sequence through the presumed (normal) start ATG codon and ends at V84.” (p. 259, and Fig. 3; partially captured here for convenience).
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Peng teaches the amino acid sequence of maize D8 (Fig. 2), which is the same as the instant SEQ ID NO: 76 (see sequence alignment below with SEQ ID NO: 76 as query (QY)).
RESULT 1
DWRF8_MAIZE
ID DWRF8_MAIZE Reviewed; 630 AA.
AC Q9ST48; Q93V57; Q93VT0; Q93VT1; Q93VT2; Q93WG1; Q93WI7; Q945I5; Q945I6;
AC Q945I7; Q945I8; Q945I9; Q945J0; Q945J1; Q945J2; Q945J3; Q945J4; Q945J5;
AC Q945J6;
DT 22-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 10-FEB-2021, entry version 97.
DE RecName: Full=DELLA protein DWARF8;
DE Short=Protein dwarf-8;
GN Name=D8;
OS Zea mays (Maize).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; Liliopsida; Poales; Poaceae; PACMAD clade;
OC Panicoideae; Andropogonodae; Andropogoneae; Tripsacinae; Zea.
OX NCBI_TaxID=4577;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS D8-D1 55-ASP--LYS-59 DELINS
RP GLY AND D8-2023 87-LEU--ASP-98 DEL.
RX PubMed=10421366; DOI=10.1038/22307;
RA Peng J., Richards D.E., Hartley N.M., Murphy G.P., Devos K.M.,
RA Flintham J.E., Beales J., Fish L.J., Worland A.J., Pelica F., Sudhakar D.,
RA Christou P., Snape J.W., Gale M.D., Harberd N.P.;
RT "'Green revolution' genes encode mutant gibberellin response modulators.";
RL Nature 400:256-261(1999).
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Query Match 100.0%; Score 3228; DB 1; Length 630;
Best Local Similarity 100.0%;
Matches 630; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MKREYQDAGGSGGDMGSSKDKMMAAAAGAGEQEEEDVDELLAALGYKVRSSDMADVAQKL 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MKREYQDAGGSGGDMGSSKDKMMAAAAGAGEQEEEDVDELLAALGYKVRSSDMADVAQKL 60
Qy 61 EQLEMAMGMGGVGGAGATADDGFVSHLATDTVHYNPSDLSSWVESMLSELNAPPAPLPPA 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 EQLEMAMGMGGVGGAGATADDGFVSHLATDTVHYNPSDLSSWVESMLSELNAPPAPLPPA 120
Qy 121 TPAPRLASTSSTVTSGAAAGAGYFDLPPAVDSSSSTYALKPIPSPVAAPSADPSTDSARE 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 TPAPRLASTSSTVTSGAAAGAGYFDLPPAVDSSSSTYALKPIPSPVAAPSADPSTDSARE 180
Qy 181 PKRMRTGGGSTSSSSSSSSSMDGGRTRSSVVEAAPPATQASAAANGPAVPVVVVDTQEAG 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 PKRMRTGGGSTSSSSSSSSSMDGGRTRSSVVEAAPPATQASAAANGPAVPVVVVDTQEAG 240
Qy 241 IRLVHALLACAEAVQQENFSAAEALVKQIPMLASSQGGAMRKVAAYFGEALARRVYRFRP 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 IRLVHALLACAEAVQQENFSAAEALVKQIPMLASSQGGAMRKVAAYFGEALARRVYRFRP 300
Qy 301 PPDSSLLDAAFADLLHAHFYESCPYLKFAHFTANQAILEAFAGCRRVHVVDFGIKQGMQW 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 PPDSSLLDAAFADLLHAHFYESCPYLKFAHFTANQAILEAFAGCRRVHVVDFGIKQGMQW 360
Qy 361 PALLQALALRPGGPPSFRLTGVGPPQPDETDALQQVGWKLAQFAHTIRVDFQYRGLVAAT 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 PALLQALALRPGGPPSFRLTGVGPPQPDETDALQQVGWKLAQFAHTIRVDFQYRGLVAAT 420
Qy 421 LADLEPFMLQPEGDDTDDEPEVIAVNSVFELHRLLAQPGALEKVLGTVRAVRPRIVTVVE 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 LADLEPFMLQPEGDDTDDEPEVIAVNSVFELHRLLAQPGALEKVLGTVRAVRPRIVTVVE 480
Qy 481 QEANHNSGTFLDRFTESLHYYSTMFDSLEGAGAGSGQSTDASPAAAGGTDQVMSEVYLGR 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 QEANHNSGTFLDRFTESLHYYSTMFDSLEGAGAGSGQSTDASPAAAGGTDQVMSEVYLGR 540
Qy 541 QICNVVACEGAERTERHETLGQWRSRLGGSGFAPVHLGSNAYKQASTLLALFAGGDGYRV 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 QICNVVACEGAERTERHETLGQWRSRLGGSGFAPVHLGSNAYKQASTLLALFAGGDGYRV 600
Qy 601 EEKDGCLTLGWHTRPLIATSAWRVAAAAAP 630
||||||||||||||||||||||||||||||
Db 601 EEKDGCLTLGWHTRPLIATSAWRVAAAAAP 630
Thus, as revealed by Peng, the D8-mpl and D8-1 alleles of Winkler are genetic modifications of the DELLA domain in the polypeptide as set forth in SEQ ID NO: 76, and as taught in Winkler, resulted in the elite maize plant having those alleles with plant height “reduced to up to 30%” (D8-1) or “reduced by up to 30%” (D8-mpl). Peng teaches that height reduction has been associated with yield increases and yield stability in a number of different crop species3. Dwarfng mutant alleles of GAI, Rht-1 or d8 can now be used directly to reduce the height of diverse crops (). Peng teaches inserting a single, genetically dominant, potentially yield-enhancing, dwarfing gene into the genome of any transformable crop (p. 260); knowing that that Arabidopsis GAI, wheat Rht-1 and maize d8 are functional orthologues. Peng further teaches range of different N-terminal deletions and truncations convert GAI/Rht-B1a/Rht-D1a/d8 into mutant repressors that are less affected by gibberellin than the normal protein. The fact that different dominant mutant alleles of Rht-1 and d8 confer differing severities of dwarfism indicates that one of the functions of GAI/RGA/Rht-B1a/Rht-D1a/d8 may be to modulate the gibberellin dose-response. Different N-terminal deletions and truncations may differentially alter the magnitude of response to a given gibberellin dose (p. 260).
Winkler and Peng do not teach the introducing these alleles through a targeted site-directed modification at the D8 genomic locus.
Feng teaches targeted modification of Arabidopsis GAI gene. As well known in the art, GAI is orthologous to maize D8 (see for example, Peng at p. 256, left, top, “maize dwarf-8 (d8) are orthologues of the Arabidopsis Gibberellin Insensitive (GAI) gene.”).
Feng teaches using CRISPR/Cas to mediate targeted site-directed modification of GAI (p. 1229, right column), using gRNA designed to target a GAI sequence located in the DELLA domain; and that more than a quarter of the GAI-modified plants showed a dwarf phenotype (Figure 1D), and at later stages, some continued to exhibit a dwarf phenotype that was similar to gai mutant plants (p. 1231, left column, para. 2). Feng teaches that the DELLA domain is important for GA-induced degradation of the GAI protein., and it is known that amino acid substitutions or deletions in the DELLA domain of GAI would result in insensitivity to GA-induced degradation, leading to a dwarf phenotype (p. 1231, left column, para. 2).
Feng also teaches CRISPR/Cas-mediated gene editing in the monocot crop plant rice with success (p. 1231, left column, para. 2).
At the time of the instant application, CRISPR/Cas-mediated gene editing has also been successfully deployed in the monocot crop plant maize. For example, Char teaches CRISPR/Cas9 for high-frequency targeted mutagenesis in maize (Abstract) B73 inbred line (p. 262). Char teaches designing two gRNAs targeting the gene-to-be-modified to increase (presumably double) the success rate or improve the possibility that at least one gRNA will be active for mutagenesis, and that this 2-gRNAs-for-1-gene approach enables large deletion mutation in the targeted gene (p. 265, right, para. 2). Char also demonstrated the successful generation of various deletions, and insertions, of various size (1 nucleotide to 182, for example; see Figs. 2, 3, and 4.).
Furthermore, Char also teaches that following DNA cleavage mediated by CRISPR/Cas, HDR can be exploited for precise sequence or gene replacement or insertion by providing a donor DNA template with sequence homology to the predicted DSB region (p. 257, right, para. 1).
Therefore, it would have been prima facie obvious to a person having ordinary skills in the art at the time of the instant application, to have utilized the targeted modification methods of Feng and Char, to introduce targeted modification to the DELLA domain of maize D8 gene in an elite maize germplasm such as B73, to arrive at the instantly claimed method.
The PHOSITA would have designed any pair of gRNAs targeting the DELLA region of maize D8, such that the gRNAs corresponding to SEQ ID Nos: 62 and 63 would be obvious design choices, given the teachings of Char, and the routine technologies available to prdinary skilled artisans such as Char regarding gRNA design at the time of the instant invention. Moreover, as discussed above, the claims do not actually even require gRNAs corresponding to SEQ ID Nos: 62 and 63.
The PHOSITA would have been motivated to practice such a method of introducing targeted genetic modification of DELLA domain in the maize D8 gene in an elite maize line. Firstly, Peng teaches that mutant GAI orthologues could be used to increase yield in a wide range of crop species. As Peng teaches, such modification would work toward a single, genetically dominant, potentially yield-enhancing, dwarfing gene in the genome of any crop, “without the need for long-term conventional breeding programs and with minimal disruption of genetic background” (p.260). Further, Char teaches that null-segregants having gene-specific mutations, but free of the Cas9/gRNA transgene, can be used for further fundamental and applied research, with minimal or no regulatory and containment requirements; and that this Maize CRISPR system will empower the public research community and accelerate the exploration of both gene function and trait improvement. Thus, even if the purpose is to study the finer details of gene function and potential trait improvement, the PHOSITA would have ample motivation to practice the method of targeted D8-DELLA medication as claimed.
The PHOSITA would have reasonable expectation of success in practicing the method as instantly claimed and arriving at the modified plants with the height reduction. Given the structural features of DELLA proteins disclosed in the specification and known in the art, one of ordinary skill in the art can readily identify the DELLA domain of the maize D8 genomic locus and introduce genetic modifications using genome editing protocols that are also known in the art. As shown in Peng and Winkler, various alleles of D8 with mutations in the DELLA domain have been known to cause plant height reduction to the degree as claimed. Based on the teachings and success of Feng and Char, the PHOSITA would have reasonable expectation of success in arriving the gRNAs targeting maize D8 DELLA domain, such as those corresponding to SEQ ID NO: 62 and 63, which are obvious design choices; and arriving at introducing various alleles in DELLA domain, such as those defined by D8-1 or D8-mpl, e.g., with HDR-mediated precise sequence or gene replacement.
Therefore, the claimed invention is prima facie obvious in view of the combined teachings of the prior art.
Claims 1-4 are rejected under 35 U.S.C. 103 as being unpatentable over Thomas (Journal of Experimental Botany 68.3 (2017): 354-358. Published: 15 February 2017) with evidence from Lanning ((2012), Crop Science, 52: 1145-1152) in view of Wang (Plant cell reports 36.3 (2017): 391-398. Published online: 3 February 2017), and Song (Journal of Plant Biotechnology 44.2 (2017): 107-114. Accepted : 2017.06.21; Published: 2017.06.30)
Thomas teaches wheat Reduced height-1 (Rht-1) genomic locus which encodes a polypeptide having DELLA domain involved in GA signaling. Thomas teaches wheat Rht-B1b and Rht-D1b semi-dwarfing alleles, that are responsible for the so called “Green Revolution” of the 20th century, when intensive agronomic practices to increase wheat grain yields could only be fully achieved when combined with varieties containing Reduced height (Rht) dwarfing genes. Thomas teaches the beneficial effects of these dwarfing alleles on grain yields are twofold: first, they prevent excessive stem elongation in response to high nitrogen fertilizer regimes that are prone to make the crop susceptible to environmental damage through lodging. Second, they allow a higher proportion of photosynthate to be partitioned to the grain by increasing the number of grains within the spikelets of the spike. The most widely utilized Rht dwarfing genes in worldwide wheat breeding programmes are those containing lesions at the Rht-1 locus. These include the Rht-B1b and Rht-D1b semi-dwarfing alleles which, at around the turn of the last century, were estimated to be present in over 70% of wheat cultivated worldwide.
Although Thomas does not mention the plant height of wheat plants carrying the Rht-B1b and Rht-D1b semi-dwarfing alleles, it is evidenced from, for example, Lanning ((2012), Crop Science, 52: 1145-1152) that either Rht-B1b and Rht-D1b alleles reduce the plant height by ~19-20% compared with near-isogenic tall controls (Table 2, and p. 1148 “Lines containingRht-B1b were 19% shorter than wild-type lines while Rht-D1b lines were 20% shorter than the wild-type based on means over the four parents”).
Thomas teaches CRISPR/Cas-based mutagenesis offering exciting prospect of unlocking the genetic diversity.
Wang teaches using CRISPR/Cas9 genome-editing platforms will facilitate the genetic modulation of plant height by altered GA pathway such as the editing of Arabidopsis GA signaling gene GAI with the CRISPR/Cas9 system results in a dwarf phenotype.
Song further teaches CRISPR/Cas9 was successfully adapted in plants, and accumulating evidence of its feasibility has been reported in model plants and major crops; HDR can lead to gene knock-ins as precise sequence alterations for gene replacement conferring gain-of-function; that enable precise and efficient base replacement in the target locus, rather than stochastic disruption of the gene, will greatly facilitate precision plant molecular breeding; base editing that conferred novel functionality that is more powerful than the former CRISPR/Cas9 version, wherein it can directly convert irreversibly one target DNA base into another without DSB or a donor template. Song further teaches successful precise gene editing in many crop and plant species including wheat (Tables 1 and 2).
Therefore, it would have been prima facie obvious for a PHOSITA to have adopted the advanced technology of targeted genetic modification such as the CRISPR/Cas9 genome-editing platforms of Song and Wang to edit the GA pathway genes in major crops such as the RHT1 gene in wheat as taught by Thomas, to arrive at the claimed method. A PHOSITA would have motivation to combine given the teachings of Thomas and Song. The PHOSITA would have had reasonable expectation of success in arriving at the historically proven RHT1 alleles that resulting in semi-dwarfism (e.g., 19-20% reduction in height) with increased yield.
Therefore, the claimed invention as a whole is prima facie obvious over the combined teachings of the prior art.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-9 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 51 and 88 of copending Application No. 16/634,275 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The copending claims are drawn to a method of reducing an elite maize plant height, the method comprising introducing one or more nucleotide modifications through a targeted site-directed modification at a genomic locus of the elite maize plant, wherein the genomic locus comprises a polynucleotide involved in gibberellic acid signaling that encodes a polypeptide comprising an amino acid sequence that is at least 95% identical to the polypeptide sequence of SEQ ID NO: 76, and wherein the one or more introduced genetic modifications modify the DELLA domain of the encoded polypeptide in the genomic locus corresponding to a target region represented by SEO ID NOs: 62 and 63, and wherein the elite maize plant height is reduced up to about 30% compared to a control elite maize plant not comprising the one or more introduced genetic modifications when the elite maize plant is heterozygous for the one or more introduced genetic modifications. As such, the copending claims are drawn to a species or subgenus of the instantly claimed.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
NO claims are allowed.
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WEIHUA . FAN
Primary Examiner
Art Unit 1663
/WEIHUA FAN/Primary Examiner, Art Unit 1663
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