DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Application
2. Claims 13, 14, 17, and 19-23 are pending and examined.
3. All rejections of claims 15, 16 and 18 are moot in view of their cancelation by Applicant.
4. The rejection of claim 21 under 35 U.S.C. 102(a)(1) is withdrawn in view of Applicant’s amendment to the claim.
5. The objections to claim 17 are withdrawn in view of Applicant’s amendments to the claim.
Claim Rejections - 35 USC § 112(b)
6. 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.
7. Claims 13, 14, 17, and 19-23 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 pre-AIA the applicant regards as the invention. This rejection has been modified in view of Applicant’s amendments to the claims. Applicant’s arguments submitted on October 6, 2025 have been fully considered but they are not persuasive.
In claim 13, line 7, the recitation “a plant having A205V and G654E substitutions acting individually” renders the claim indefinite. The phrase refers to the “predicted additive resistance … exhibited by a plant,” which plant is an apparent point of reference for the plant comprising “combined A205V and G654E” substitutions. Since both plants are required to comprise both substitutions, it is unclear how they differ or how the mutations would be considered as “acting individually” in a plant that comprises both. Claim 22, as instantly amended, is indefinite for the same reason.
In claims 13, 17 and 22, the terms “A205V” and “G654E,” without a clear reference sequence, render the claim indefinite, because while the numbers in “A205V” and “G654E” appear to refer to the standard Arabidopsis numbering of the AHASL residues, the claims recite either “a monocot” or “rice” and appear to refer to said substitutions as being present in said monocot or rice plant. It is thus unclear what structure or structures the “monocot” or “rice” plant are meant to comprise. Although, as instantly amended, the claims recite the corresponding positions in rice, it does not overcome the issue, because a reference sequence is still missing.
In claim 17, the phrase “wherein the synergistic resistance is greater than a predicted additive resistance of the A205V and the G654E substitutions acting individually” introduces further ambiguity into the claim language because it does not refer to a rice plant or plants, which makes it unclear what control the claim is meant to recite.
Claim 17 is indefinite for the following additional reason. While the claim is drawn to a method for controlling weeds in a rice field, the active method steps do not recite applying herbicide to weeds nor mention any weeds. It is thus unclear how the method should be practiced.
The phrasing of claim 21 renders the claim indefinite because it is unclear whether the newly added clause that begins with “that exhibits” refers to the “progeny” or the “rice plant.” And it is unclear whether or not the “progeny” is meant to comprise the mutant AHAS.
Given that claims 14 and 19-23 depend from claims 13 or 17 and fail to recite additional limitations overcoming their indefiniteness, said dependent claims are indefinite as well.
Response to Arguments
Applicant argues that the amendments to the claims overcome the rejection (page 5 of the Remarks). This is not found to be persuasive. While Applicant’s amendments are acknowledged and the rejection has been modified accordingly, the claims remain indefinite for the reasons set forth above.
Claim Rejections - 35 USC § 112(d)
8. The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
9. Claim 23 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
The claim recites product-by-process limitations that specify the mutagenesis methods via which the A205V and the G654E substitutions were introduced into the AHAS. These recitations do not limit the structure of the rice plant used in the method of claim 22 or of any nucleic acids comprised in said plant. This is because the structure of a nucleic acid is determined by its nucleotide sequence and does not depend on its method of production. See MPEP 2113. Consequently, claim 23 fails to properly further limit the claim from which it depends.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Interpretation
10. The following is noted with regard to claim interpretation. As set forth above, the claims were found indefinite. For the purpose of the examination, the claims are given their broadest reasonable interpretation as follows.
In claim 13, the AHAS amino acid position numbers are read as referring to the Arabidopsis numbering of the residues. The plain language of the claim recites a nucleic acid encoding a double-mutated AHAS, comprising the A205V and the G654E substitutions on the same enzyme molecule. The claim is read to encompass a monocot plant comprising said double-mutated AHAS, whether endogenous to said monocot plant or not.
Claim 17 is reasonably interpreted as requiring the application of an herbicide to the weeds and/or the herbicide tolerant rice plant growing in a rice field.
Claim 21 would encompass the progeny of the rice plant of claim 22 of any filial generation, wherein said progeny comprises the mutated AHAS.
Claim 22 requires “combining” a rice genome having an AHAS with the A205V substitution with a rice genome having an AHAS with the G654E substitution. The wording of the claim, including the use of the open-ended transitional term “having,” is given its broadest reasonable interpretation as comprising crossing two rice plants, each of which comprises both substitutions.
Claim Rejections - 35 USC § 103
11. 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 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.
12. 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.
13. Claims 13, 14, 17 and 19-22 remain and claim 23 is rejected under 35 U.S.C. 103 as being unpatentable over Livore et al (US Patent Publication 20100029485, published February 3, 2010), in view of Roso et al (Field Crop Res. (2010) 119:175-182) and Okuzaki et al (Plant Cell Rep. (2004) 22:509-512). Applicant’s arguments submitted on October 6, 2025 have been fully considered but they are not persuasive.
The claims are drawn to a monocot plant tolerant to AHAS inhibitor herbicides, wherein said tolerance is associated with two substitutions in the AHAS enzyme: the A205V and G654E, and to the methods of using said plants.
Livore et al teach a rice plant comprising at least one copy of a rice AHASL polynucleotide that encodes a herbicide resistant AHASL protein, wherein said protein comprises an A205V substitution (A179V, in rice numbering). Livore et al teach a seed of said plant, and teach that the plant has enhanced tolerance to at least one class of AHAS inhibiting herbicides (claims 1-14; Examples 1 and 2; see also paragraphs 0014-0018). Livore et al teach that the A205V substitution occurs in one of the conserved domains of the AHAS enzyme (Table 2). Livore et al expressly suggests using the rice AHASL molecules of their invention to introduce an additional one or more substitutions, including wherein the substitutions are selected from the known substitutions, including S653N and A205V, among others (paragraph 0055).
Livore et al teach obtaining the rice plants comprising the A205V substitution using the sodium azide mutagenesis and selection of a known rice cultivar (Example 1). Livore et al teach the nucleic acid and the amino acid sequences of the wild type and mutant rice AHASL (Figures 1 and 2). Livore et al teach that the resultant rice plants were tolerant to two applications of 1x rates of imazapyr and imazapic (paragraph 0207).
Livore et al teach methods for controlling weeds in the vicinity of the herbicide resistant plants of their invention. Livore et al teach said method wherein the weed is red rice and other weeds sensitive to imidazolinones (paragraphs 0023, 0033; claims 15-16). Livore et al teach various application methods and formulations used in the methods of weed control (paragraph 0129).
Livore et al teach methods for producing a herbicide resistant rice plant through conventional plant breeding including crossing two plants resistant to the same or different herbicides (paragraphs 0131 and 0132).
Livore et al do not teach a rice plant comprising an AHAS enzyme comprising the G654E substitution in addition to the A205V one.
Roso et al teach a rice cultivar IRGA 422 CL that comprises a mutant AHAS with the G654E substitution (Abstract). Roso et al teach that said cultivar is one of the main cultivars in Brazil (pg. 180, left col). Roso et al teach the gene sequences for the mutant AHAS and teach identifying the G654E substitution was found in the vast majority of herbicide tolerant red rice plants as well. Roso et al teach that the substitution was found in red rice, alone or in combination with other known substitutions (see Introduction on pg. 175-176; pg. 176 right col.; Fig. 3; Table 3). Roso et al teach that the levels of imidazolinone tolerance conferred by the G654E substitution to cultivated and red rice was lower than those conferred by the other substitutions (pg. 181, left col.).
Okuzaki et al teach successfully using site-specific oligonucleotide-based mutagenesis to introduce point mutations into the rice AHASL gene (Okuzaki et al, Abstract and Introduction). Okuzaki et al teach that the oligonucleotide-directed gene targeting is thought to be less complicated in rice than in tobacco or maize (Okuzaki et al pg. 512, left col.).
At the time of filing, it would have been prima facie obvious to modify the rice plant of Livore et al, using the method of Okuzaki et al, and introduce the G654E substitution, taught by Roso et al, onto the rice AHASL. Alternatively, it would have been obvious to introduce the A205V substitution onto the rice AHASL of Roso et al, which already comprises the G654E substitution. The resultant rice plant would read on the plant of claims 13-16 as well as on the progeny recited in claim 21, given the above claim interpretation.
It would have been also prima facie obvious to use the resultant plant in a method of weed control, such as the method taught by Livore et al, by applying an imidazolinone to the plant and weeds in the vicinity of the plant, wherein both the weeds and the plants are in a field (instant claims 17-20).
It would have been obvious to use the plant in a breeding program, as suggested by Livore et al. A cross between the two plants each comprising the A205V and G654 substitutions would read on the active step of the method of claim 22, in view of the above claim interpretation. In addition, given the teachings of Livore et al, it would have been obvious to cross a plant comprising the A205V substitution with another plant comprising a different known herbicide tolerance AHAS substitution such as the plant of Roso et al, comprising the G654E substitution. Doing so would also read on the active step of the method.
One would have been motivated to combine the above teachings for the following reasons. First, Livore et al expressly suggest combining the A205V substitution with one or more substitutions located in other conserved domains of the AHASL, including with a substitution located in Domain E (S653E), which domain comprises relative position 654 as well. Second, while both A205V and G654E confer tolerance to imidazolinones, as taught in Livore et al and Roso et al, the level of tolerance conferred by the G654E substitution is relatively low. Thus, one would be motivated to introduce the A205V substitution into the cultivar of Roso et al, for example, in order to enhance tolerance to imidazolinones. Third, as taught by Roso et al, the G654E substitution is found in the majority of red rice plants that are resistant to imidazolinones, wherein red rice, a common weed, appears to have acquired the AHASL comprising said substitution from the cultivated rice variety. Thus, combining the A205V and the G654E substitutions in the same rice plant, and consequently ensuring higher tolerance to imidazolinones, would enable one to more effectively control imidazolinone tolerant populations of red rice.
Given that Okuzaki et al successfully reduced their method to practice, given the conserved nature of the domain, where position 654 is located, and given the known tolerance properties of both A205V and G654E substitutions, one would have had reasonable expectation of success.
With regard to the synergistic level of tolerance, it is noted that, given that the structure of the claimed monocot plant would have been prima facie obvious, the property of tolerance would have naturally flowed from said obvious structure. “The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious.” Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). Moreover, given the fact that both substitutions, A205V and G654E confer tolerance to imidazolinones, but are located in different conserved domains of the enzyme; it would not have been unexpected that at least under some conditions, all of which are encompassed the by claims, the double mutant would have a greater than additive level of tolerance.
Response to Arguments
Applicant argues that “Livore, Roso, and Okuzaki, alone or in combination, fail to teach a rice plant having mutant AHAS enzyme having the recited combination of the A205V and G654E amino acid substitutions, nor do the references teach or suggest the unexpected, synergistic herbicide resistance demonstrated by said combination. Specifically, the claimed combination of mutations confers unexpectedly dramatic synergistic resistance to AHAS inhibitor that is far greater than (i) the AHAS inhibitor resistance provided by a plant having either of the individual mutation and (ii) the additive resistance expected of a plant carrying both mutations, as called for in the pending claims” (page 7 of the Remarks).
Applicant cites Examples 1 and 2 and argues that “the claimed combination of mutations imparts AHAS inhibitor resistance that is far greater than a predicted additive resistance of a plant carrying both mutations. This is illustrated in Example 4 and Figure 10 of the specification.” Applicant argues that the “specification provides a formula that calculates the expected degree of synergistic resistance” (pages 7-8 of the Remarks).
Applicant argues that “even if one of ordinary skill in the art had considered specifically combining the A205V and G654E substitutions in a rice plant, he or she would have expected, at best, an additive effect, and probably a negative effect because these mutations affect the same enzyme and are in the same gene. Not all combinations of amino acid mutations in the AHAS enzyme will achieve the observed enhanced, synergistic resistance, and some might even have a negative effect, such as a reduction of plant fitness. Yet, the improved resistance of the presently claimed mutations is unexpectedly achieved without deleterious effects on plant fitness or other traits such as crop yield. Okuzaki fails to cure the above deficiencies identified in Livore and Roso. The Examiner cites Okuzaki as teaching site-specific oligonucleotide-based mutagenesis to introduce point mutations in AHAS enzyme in rice. As described in the specification and as presently claimed, the claimed rice plant introduces independent A205V and G654E mutations in the parent lines via a chemical mutagenesis process that induces random single-base nucleotide changes in the DNA” (pages 9-10 of the Remarks, citations in the original omitted). Applicant argues that the method of Okuzaki et al would not have been expected “to result in a significant number of rice plants modified to possess both of the claimed A205V and G654E mutations” (page 10 of the Remarks).
Applicant’s argument is not found to be persuasive. Regarding the argument directed to the unexpected results, MPEP 716.02 explains that “any differences between the claimed invention and the prior art may be expected to result in some differences in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected. In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (differences in sedative and anticholinergic effects between prior art and claimed antidepressants were not unexpected). When a greater than expected result is alleged, a greater than additive effect is not necessarily sufficient to overcome a prima facie case of obviousness because such an effect can either be expected or unexpected. Applicants must further show that the results were greater than those which would have been expected from the prior art to an unobvious extent, and that the results are of a significant, practical advantage. Ex parte The NutraSweet Co., 19 USPQ2d 1586 (Bd. Pat. App. & Inter. 1991). In the instant case, Applicant has not supplied sufficient evidence to show that the results would have been greater than expected “to an unobvious extent,” for the following reasons.
Applicant argues above that in combining the two substitutions at issue, one “would have expected, at best, an additive effect, and probably a negative effect because these mutations affect the same enzyme and are in the same gene.” Applicant supplies no explanation as to why, from the premise that both mutations are “in the same enzyme and are in the same gene,” one would have arrived at the conclusion that at best an additive effect would be expected. This position is also contradicted by the teachings of the prior art regarding, specifically, AHAS, including in rice. Kawai et al, for example, teach that the presence, in the same rice AHAS (referred to by its synonym, “ALS”) a substitution at W548 or S627 together with a substitution at P171 (in the rice numbering) resulted in “synergistic resistance” to AHAS inhibiting herbicides (J. Pestic. Sci. (2008) 33:128-137; Abstract; pg. 135, right col.). Consistent with the teachings of Kawai et al, Walter et al teach that two substitutions present on two different domains and expressed by different alleles of the AHAS (P197S on ALS1 and W574L on ALS2), resulted in synergistic level of tolerance in soybean plants (Pest Management Science (2014) 70:1831-1839). The teachings of Walter et al are particularly relevant to the instant claim 22, which is drawn to a method of making a rice plant comprising the two substitutions at issue on different alleles.
Moreover, the biochemical properties of G654 and A205 are consistent with the expectation of synergistic effect towards herbicide tolerance, when mutated. Glycine 654 is located in the inhibitor-binding site of the enzyme and is specific towards imidazolinones: it is not involved in binding sulfonylureas (see Duggleby et al, Plant Physiol. (2008) 48:309-324). Given that alanine 205 is also involved in imidazolinone binding at the herbicide binding site, one would reasonably expect that the weakening of imidazolinone binding produced by a substitution at G654 would further weaken the binding of the herbicide at the other site (see Duggleby et al, pg. 319, left col.; pg. 321, right col.). Whether the mutations were present on the same or on two different alleles would not affect this reasoning because the active site of AHAS is formed by two monomers (Duggleby et al, pg. 315, right col.).
Next, even assuming, for the sake of the argument, that a showing of unexpected results was made, it would not be sufficient to overcome the rejection because it would not be commensurate with the scope of the claims. While claim 13, for example, encompasses the property of “synergistic resistance” to any AHAS inhibitor in any monocot plant, the teachings of the specificaiton are limited to tolerance to imazethapyr and imazapic/imazapyr applications, in rice plants (Examples 1-4). It is noted that “objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support.” In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980). MPEP 716.02(d).
It is also noted that while the showing of unexpected results must be of both statistical and practical significance, neither the specifications nor the figures themselves appear to provide standard deviation for the figures that aim to show unexpected results, such as Figure 4. See Ex parte Gelles, 22 USPQ2d 1318, 1319 (Bd. Pat. App. & Inter. 1992). MPEP 716.02(b).
The Examiner also notes that the structure of a rice plant that would read on the plant of the instant claims would have been prima facie obvious. Applicant has not disputed the obviousness of making that structure. The specific property of tolerance would have naturally flowed from said prima facie obvious structure. “The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious.” Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
Applicant’s argument directed to the teachings of Okuzaki et al is not found to be persuasive either. First, one would not have had to use the method of Okuzaki et al to introduce both mutations at issue into a rice AHASL, but only one, because the plants of Roso et al already comprise the G654E substitution. Second, the fact that the method of Okuzaki et al might not operate with high efficiency does not in any way make it inoperable. It is well-established that efficacy is not required for prior art enablement. MPEP 2121(II); "Proof of efficacy is not required for a prior art reference to be enabling for purposes of anticipation." Impax Labs. Inc. v. Aventis Pharm. Inc., 468 F.3d 1366, 1383, 81 USPQ2d 1001, 1013 (Fed. Cir. 2006) (citing Rasmusson v. SmithKline Beecham Corp., 413 F.3d 1318, 1326, 75 USPQ2d 1297, 1302 (Fed. Cir. 2005)). The rejection is maintained.
Conclusion
14. No claims are allowed
15. 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.
16. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MYKOLA V KOVALENKO whose telephone number is (571)272-6921. The examiner can normally be reached Mon.-Fri. 9:00-5:30 PST.
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/MYKOLA V. KOVALENKO/Primary Examiner, Art Unit 1662