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, 2, 4, 6-10, 12-15, 19, and 17-20 are pending.
3. Claims 1, 2, 4, 6-10, 12-14, and 20 are examined.
4. Claims 15 and 17-19 remain withdrawn.
5. The rejection of claims 1, 2, 4, 6-10, 12-14 and 16 under 35 U.S.C. 112(b) is withdrawn in view of Applicant’s amendments to the claims.
6. All rejections of canceled claims 5 and 16 are moot.
Election/Restrictions
7. 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Claim 15 remains withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Invention, there being no allowable generic or linking claim.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 For that reason, the claims remain withdrawn from consideration as being drawn to non-elected species.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 new claim 20, however, would have been included in the elected Group, and is thus examined herein.
Claim Objections
8. Claim 20 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. The term “Seq ID No: 89” should be capitalized to recite “SEQ ID NO: 89” for consistency. Appropriate correction is required.
Improper Markush Grouping
9. Claims 1 and 12 remain 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 January 17, 2025 were fully considered but they are not persuasive.
The Markush grouping of claim 12 is improper because the alternatives defined by the Markush 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: 3-50, which 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 newly 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 the recites HPPD mutants belong to the same class of enzymes, and that they are “all mutant HPPDs and therefore share substantial use as well” (page 6 of the Remarks).
This is not found to be persuasive. Applicant’s amendments are not sufficient to overcome the instant rejection. 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). The rejection is maintained.
Claim Rejections - 35 USC § 112(b)
10. 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.
11. Claim 20 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The term “combinations thereof,” renders the claim indefinite because its antecedent is unclear. For example, if Applicant meant for the term to refer to the combination of SEQ ID NO: 89 and 90, the term should be used in singular, because there is only one combination possible. If the term is meant to refer to another combination of previously recited elements, it should be clearly indicated in the claim. In its current wording, the metes and bounds of the claim are unclear.
Claim Rejections - 35 USC § 112(d)
12. 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.
13. Claim 2 remains 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. This rejection has been modified in view of Applicant’s amendments to the claims Applicant’s arguments submitted on January 17, 2025 have been fully considered but they are not persuasive.
Claim 2 is drawn to the method of claim 1, wherein “the mutant HPPD enzyme is less sensitive to HPPD inhibitors than the native HPPD enzyme before mutation.” However, claim 1, already requires a mutant HPPD that comprises one of the substitution combinations, which substitutions would necessarily result in herbicide tolerance, as admitted in the specificaiton, and well-known in the prior art (see, for example, Dubald et al, discussed in the Non-Final Office Action mailed on November 20, 2023; see also Boudec et al, US Patent 6,245,968, col. 1-4; Examples 1-2). The dependent claim thus recites the property inherent in the method of claim 1, and for that reason, 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.
Response to Arguments
Applicant argues that the amendments to the claims overcome the rejection (page 7 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 rejected for the reasons set forth above.
Claim Rejections - 35 USC § 112(a)
14. 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
15. Claims 1, 2, 4, 6-10, 12-14 and 16 remain rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The 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 October 29, 2025 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.
Scope of Enablement
16. Claims 1, 2, 4, 6-10, 12-14, and 16 remain rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a 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’s argument appears to be directed to both, the written description and the scope of enablement rejections. Applicant argues that “a person of skill in the art would understand how to make and use the full scope of the claimed methods without undue experimentation. Examples in the specification demonstrate that reducing endogenous HPPR gene expression results in an increase of tolerance to a [HPPD] inhibitor herbicide. There is enough literature available that teaches a person skill in the art features for identifying a plant having an endogenous HPPR gene. In view of the amended claims, and in view of submissions made in response to the previous office actions, Applicant submits that any person skilled in the art would be able to make or use the invention in commensurate in scope with the amended claims” (page 8 of the Remarks).
Applicant’s argument regarding the teachings of the instant specifications and the prior art were considered in detail in the previous Office Actions and remain not persuasive for the reasons of record.
Specifically, while HPPR may be widely distributed in plants, that teaching is not sufficient to enable the instant invention through the full scope of the claims. This is because the art also 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). In view of this, 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.
Moreover, the invention also remains not sufficiently described, for the reasons set for the above. The rejections are maintained.
Conclusion
17. No claims are allowed.
18. THIS ACTION IS MADE FINAL. 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.
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/MYKOLA V. KOVALENKO/Primary Examiner, Art Unit 1662