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 Claims
2. Claims 1, 4, 6-10, 12-15, 19, and 17-25 are pending.
3. Claims 1, 4, 6-10, 12-14, 20, and 21 are examined.
4. Claims 15 and 17-19 remain and claims 22-25 are withdrawn.
5. The objections to claim 20 are withdrawn in view of Applicant’s amendments to the claim.
6. All rejections of the canceled claim 2 are moot in view of its cancelation by Applicant.
7. The rejection of claim 20 under 35 U.S.C. 112(b) is withdrawn in view of Applicant’s amendments to the claim.
Continued Examination Under 37 CFR 1.114
8. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on April 23, 2026 has been entered.
Election/Restrictions
9. Applicant's election with traverse of Group I, claims 1-14; part (e) of claim 4 and SEQ ID NO: 16 as species, in the reply filed on February 14, 2022 is acknowledged. Because Applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claim 15 remains withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on February 14, 2022. Previously added claims 17-19 are drawn to the method of claim 10, but read only on the non-elected species. For that reason, the claims remain withdrawn from consideration as being drawn to non-elected species. The previously added claim 20, however, would have been included in the elected Group, and was thus examined herein.
Similarly, newly added claims 22-25 read only on the non-elected species, and are withdrawn from consideration as being drawn to non-elected species. However, new claim 21 encompasses SEQ ID NO: 16, the elected species, and is thus examined to the extent it reads on that sequence.
Claim Objections
10. Claim 9 is objected to because of the following informalities. The abbreviations “HPPD” ad “HPPR” need not be spelled out given that they already were in claim 1. Appropriate correction is required.
Improper Markush Grouping
11. Claims 1 and 12 remain and claim 21 is rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 706.03(y).
This rejection has been modified in view of Applicant’s amendments to the claim. Applicant’s argument submitted on April 23, 2026 were fully considered but they are not persuasive.
The Markush grouping of claim 12 is improper because the alternatives defined by the grouping do not share both a single structural similarity and a common use for the following reasons. The grouping of claim 12 encompasses SEQ ID NO: 3, 6, 7, 8 and 16; the grouping of the new claim 21 encompasses SEQ ID NO: 4, 5, and 9-50. These sequences represent different mutant HPPDs from at least two organisms (see Sequence Listing). The sequences comprise different amino acid substitutions relative to a corresponding wild-type HPPD and do not appear to be obvious variants. Given the diverse range of mutants encompassed by the members of the grouping, they do not appear to encompass a single structural similarity. Neither do these members appears to share a common use that flows from a substantial structural feature.
The Markush grouping previously added to claim 1 is improper as well. The grouping encompasses combinations of individual amino acid substitutions. Each combination represents a structurally and functionally distinct chemical entity with different herbicide tolerance profiles (see, for example Boudec et al, US Patent 6,245,968, col. 1-4; Examples 1-2). For this reason, the members of the grouping do not share a common structural feature and a common use that flows from that structural feature.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Response to Arguments
Applicant argues that the claims have been amended, and that new claims have been added to recite some of the individual species (page 5 of the Remarks).
This is not found to be persuasive. Applicant’s amendments are acknowledged and the rejection has been modified accordingly. However, the amendments were not sufficient to obviate the issue and the claims remain rejected as set forth in the modified rejection above.
The groupings continue to encompasses numerous amino acid sequences that represent different mutant HPPDs from at least two organisms. The sequences comprise different amino acid substitutions relative to a corresponding wild-type HPPD and do not appear to be obvious variants. The sequences are both structurally and functionally distinct, and cannot be said to be functionally equivalent. This is consistent with the teachings of the prior art regarding HPPD mutants (see Boudec et al, above).
With regard to the newly added claims 21-25, given the species election requirement, only claim 21 is examined and only to the extent it reads on SEQ ID NO: 16, the elected species, because claims 22-25 do not encompass any elected species.
Claim Rejections - 35 USC § 112(a)
12. The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Written Description
13. Claims 1, 4, 6-10, and 12-14 remain and claim 21 is 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.
This rejection has been modified in view of Applicant’s amendments to the claims. Applicant’s arguments submitted on April 23, 2026 have been fully considered but they are not persuasive.
Applicant claims a method for increasing tolerance to an HPPD inhibitor herbicide in a plant comprising reducing expression, from an endogenous HPPR gene, of at least one HPPR enzyme by transforming a plant cell with a DNA construct comprising an RNAi region that inhibits the expression of at least one endogenous HPPR gene and a coding region that encodes a mutant HPPD enzyme.
Applicant describes a method comprising co-expressing an RNAi construct that targets two putative HPPR genes (SEQ ID NO: 89 and 90) and a construct that expresses one mutant HPPD termed “Pf-HPPD-evo41” in soybean plant cells (Example 1). Applicant describes obtaining soybean plants from said cells, treating them with an HPPD inhibitor, “NOC115” and evaluating the effects. Applicant describes plants expressing both, the construct targeting the HPPR and expressing the mutant HPPD, were more tolerant to said inhibitor than the plants expressing the mutant HPPD construct alone (Example 2; Table 1; Figure 7). The alignment of the amino acid sequence of Pf-HPPD-evo41 against that of the wild-type HPPD shows that the mutant differs from the wild-type at four residues in the conserved C-terminus of the enzyme (Figure 2).
Applicant does not describe the genus of method encompassed by the claims. While claim 1 encompasses the targeting of any HPPR gene using RNAi, the specificaiton has described a single method comprising co-expressing an RNAi construct targeting two putative HPPR genes (SEQ ID NO: 89 and 90), at once. This is not sufficiently representative of the claimed genus. For example, the specification has not reduced to practice a method wherein only one HPPR gene is inhibited. And it is unclear from the teachings of the specification whether a method targeting a single HPPR gene would result in increased HPPD herbicide tolerance.
This is consistent with the limited teachings of the prior art regarding the HPPR. The art teaches that HPPRs comprise a family of enzymes, and it is unclear how redundant their expression is in plants (see Konishi et al, US Patent Publication 20140073024, paragraphs 0443-0448). Moreover, the instant specification admits that HPPR, although it uses the same substrate as HPPD “has been biochemically characterized only in a few plant species” (page 6, last paragraph).
Applicant has also failed to set forth the requisite structure-function relationship for the genus of constructs used in the claimed methods. For example, claims 1 and 10 encompass any and all HPPR enzymes, recited solely by function. Yet it is unclear how one would select an HPPR for targeting in the claimed method. Given from the teachings of the prior art (see Konishi et al, above), and the limited teachings of the speciation, it appears that merely setting forth the enzymatic activity of an HPPR is not sufficient to allow one to envision whether a particular enzyme could be used in the claimed methods.
For the above reasons, it is unclear whether at the time of filing, Applicant was in possession of the instant invention as broadly claimed.
Response to Arguments
Applicant argues that “The specification describes a broad genus, not a single example. It discloses dozens of specific mutant HPPD sequences with defined substitution patterns at identified positions, sourced from both bacterial and plant enzymes. These mutants are presented with structural context through alignments and identity thresholds. In addition, the specification identifies two specific soybean HPPR genes with full nucleotide and amino-acid-level disclosure, including exact dsRNA concatemer design” (page 7 of the Remarks).
Applicant argues that “Silencing HPPR increases HPP availability for HPPD, improving tolerance to HPPD inhibitors. This mechanism is grounded in known enzyme kinetics and provides a clear structure-function relationship applicable across plant species. The specification further teaches how to design dsRNA constructs targeting HPPR sequences shared across species. …Targeting a Single HPPR Gene Is Explicitly Supported” (page 7 of the Remarks).
Applicant’s argument is not found to be persuasive. The argument appears to merely summarize some of the subject matter that is described, but fails to address the actual ground for the instant rejection, which is the disparity between the scope of the claims and the subject matter that is, in fact, described. For example, the fact that one of ordinary skill in the art would have been able to envision an RNAi construct targeting a known HPPR is not in dispute. Instead, the lack of written description of the method of claim 1 stems from the fact that while Applicant has described a single scenario wherein the method comprises expressing an RNAi construct that target two putative HPPR genes (SEQ ID NO: 89 and 90) at once, claim 1 encompasses targeting any number of any endogenous HPPR genes. Moreover, contrary to Applicant’s conclusion, the recitation of “one or more” HPPR genes cannot be relied upon for description of the claimed method that targets a single gene. This is particularly true given the very limited teachings regarding the structure-function relationship for HPPRs in the specification as well as in the prior art.
The Examiner also maintains that the plain language of claims 1 and 9 indicates that the genus of HPPR’s to be targeted is recited solely by its function, with no structure (such as SEQ ID NO’s) provided.
Scope of Enablement
14. Claims 1, 4, 6-10, 12-14, and 16 remain and claim 21 is 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 method of conferring tolerance to HPPD inhibitors comprising co-expressing an RNAi construct inhibiting two putative HPPR genes of SEQ ID NO: 89 and 90, with a construct encoding a mutant Pseudomonas fluorescens HPPD of SEQ ID NO: 16, does not reasonably provide enablement for the invention as broadly claimed.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with these claims. This rejection has been modified in view of Applicant’s amendments to the claims Applicant’s arguments submitted on October 29, 2025 have been fully considered but they are not persuasive.
In re Wands, 858 F.2d 731 (Fed. Cir. 1988) lists the following eight factors for determining whether undue experimentation would be required to practice an invention: (1) quantity of experimentation necessary; (2) amount of direction or guidance supplied; (3) presence or absence of working examples; (4) nature of the invention; (5) state of the prior art; (6) relative skill of those in the art; (7) predictability or unpredictability or the prior art; (8) breadth of the claims.
Applicant claims a method for increasing tolerance to an HPPD inhibitor herbicide in a plant comprising reducing expression, from an endogenous HPPR gene, of at least one HPPR enzyme by transforming a plant cell with a DNA construct comprising an RNAi region that inhibits the expression of at least one endogenous HPPR gene and a coding region that encodes a mutant HPPD enzyme, wherein the mutant HPPD comprises the recited substitutions or wherein the coding sequence that encodes said mutant HPPD enzyme comprises SEQ ID NO: 16.
Applicant teaches co-expressing an RNAi construct that targets two putative HPPR genes (SEQ ID NO: 89 and 90) with a construct that expresses one mutant HPPD termed “Pf-HPPD-evo41” in soybean plant cells (Example 1). Applicant teaches obtaining soybean plants from said cells, treating them with an HPPD inhibitor, “NOC115” and evaluating the effects. Applicant teaches that the plants expressing both, the construct targeting the HPPR and the expressing the mutant HPPD, were more tolerant to said inhibitor than the plants expressing the mutant HPPD construct alone (Example 2; Table 1; Figure 7). The alignment of the amino acid sequence of Pf-HPPD-evo41 against that of the wild-type HPPD shows that the mutant differs from the wild-type at four residues in the conserved C-terminus of the enzyme (Figure 2).
Applicant does not teach how to practice the invention through the full scope of its claims. Both the teachings of the specification and the state of the prior art indicate that it would be unpredictable to attempt to do so without substantial further experimentation.
While the overexpression of both, mutant and wild-type HPPD (including wherein the mutant is derived from Pseudomonas fluorescens) has been extensively used to confer herbicide tolerance to crops (see, for example Boudec et al, US Patent 6,245,968, col. 1-4; Examples 1-2), the prior art appears silent with regard to the role of HPPR in conferring herbicide tolerance or its interaction with HPPD with regard to said tolerance.
HPPR has been characterized as an enzyme involved in vitamin E synthesis, which competes for substrate with HPPD (Wang et al (2017) Chinese J. Nat. Med. (2017) 917-927; paragraph spanning pg. 917-918). However, there are no teachings indicating how those characteristics would enable one to control herbicide tolerance by affecting the expression levels of the native HPPR.
In addition, while the instant specification teaches targeting two soybean HPPR genes at once (Example 1; Fig. 4), it is unclear whether targeting one of said genes would be sufficient. At the same time, the claims encompass targeting “at least one” HPPR gene. The art teaches that HPPRs comprise a family of enzymes, and it is unclear how redundant their expression is in plants (see Konishi et al, US Patent Publication 20140073024, paragraphs 0443-0448). At the same time, the instant specification admits that HPPR, although it uses the same substrate as HPPD “has been biochemically characterized only in a few plant species” (page 6, last paragraph). One of ordinary skill in the art would not be able to predictably extrapolate these limited teachings of the specification onto the genus of any plant, and any HPPR enzyme, and any HPPD inhibitor, all of which are encompassed by the broadly drawn claims.
Given limited guidance supplied by Applicant, the breadth of the claims and the nature of the invention, as well as the unpredictability in the art, it would have required one skilled in the art undue trial and error experimentation to practice the claimed invention through the full scope of its claims.
Response to Arguments
Applicant argues that the substrate competition between HPPR and HPPD is “universal and not species-specific,” that “the specification provides detailed dsRNA design parameters” and “includes both greenhouse and field data demonstrating effectiveness across chemically distinct HPPD inhibitors” (page 8).
Applicant argues that “HPPR silencing is supported by a clear mechanistic rationale, experimental data, and field validation” and argues that the specification “explicitly states that targeting HPPR genes in other species would be feasible for those skilled in the art” (page 8 of the Remarks).
Applicant’s argument is not found to be persuasive. The argument’s general statements fail to show how one would have been able to practice the instant invention through the full scope of the claims. For example, the fact that the mechanism of substrate competition between HPPR and HPPD may be identical in more than one species does not address the teaching that HPPRs comprise a family of enzymes, and it is unclear how redundant their expression and function are in plants. And since the claimed method is based on reducing the expression of a native HPPR, in order to practice it, one would need to know (either from the specification or the prior art) which HPPRs can be predictably targeted. Yet there is no way to do so based on the limited teachings of the instant disclosure and the available prior art. The Examiner notes that the instant specification admits that HPPR, although it uses the same substrate as HPPD “has been biochemically characterized only in a few plant species” (page 6, last paragraph). Applicant’s argument does not address this reasoning.
The Examiner also maintains that there are no teachings in the prior art indicating or suggesting that one could control herbicide tolerance by affecting the expression levels of the native HPPR - an enzyme that has been previously characterized as an enzyme involved in vitamin E synthesis.
For these reasons, it would be highly unpredictable to attempt to practice the instant invention through the full scope of the claims without substantial further trial and error experimentation. The rejection is maintained.
Conclusion
15. No claims are allowed.
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
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