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 .
Application Status and Election
Claims 9-11, 18, and 20-24 are currently pending. Applicant’s election of species without traverse in the oral election on June 6 day 2024 with attorney Alison Baldwin (Reg# 48968) remains acknowledged. Applicant elected the species: Gene AAEL017331, SEQ ID NO: 28 and SEQ ID NO: 29, and shRNA as the RNAi type.
Claims 18 and 22 have been amended.
Claim 24 remains withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Examination on the merits commences on claims 9-11, 18, and 20-23.
Applicants are informed that the rejections and/or objections of the previous Office action not stated below have been withdrawn from consideration in view of the Applicant' s arguments and/or amendments. Applicant’s amendments and arguments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons that follow.
Amendments to claim 18 fail to address the previous §112b rejection of record.
Examiner notes repeated attempts to communicate with attorney Alison Baldwin (Reg# 48968) and subsequent attempts to communicate for Examiner’s Amendment with replacement attorney Brett Zirkle (Reg# 77124), without success.
Claim Rejections - 35 USC § 112(b) - MAINTAINED
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 9-11, 18, and 20-23 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 18(ii) recites, “the yeast cell expressing the iRNA.”, however there is no antecedent basis for “the yeast cell” in the claims. Given that the metes and bounds of claim 18 are unclear, claim 18 is indefinite.
Claims 9-11 and 20-23 depend from claim 18 which is indefinite. Given that the metes and bounds claim 18 are unclear, this renders the metes and bounds of the dependent claims 9-11 and 20-23 also unclear, without remedying the indefiniteness. Therefore, claims 9-11 and 20-23 are also indefinite.
Allowable Subject Matter
Claims 9-11, and 20-23 are objected to as being dependent from the rejected claim 18.
A thorough search of the prior art does not teach, suggest, or provide a motivation for a mosquito insecticide composition comprising at least one iRNA ribonucleic acid, a yeast cell expressing the iRNA, and the least one suitable carrier, excipient or diluent, wherein the interfering ribonucleic acid (iRNA) corresponding to a target nucleotide sequence of at least one sex-linked larval lethal arthropod gene required for maturation from larvae to adult of at least one arthropod species, wherein one of the sex-linked larval lethal arthropod genes is AAEL017331, and wherein binding of the target nucleotide sequence by the iRNA silences expression of the at least one sex-inked gene in female larvae, wherein the at least one arthropod species consists of at least one mosquito species.
The closest prior art is Paldi, GenBankGGT1, and Flavell of record.
Paldi teaches a method produces a larvicidal composition, the method comprising introducing into a cell a nucleic acid larvicide affecting fertility or fecundity of a female mosquito, thereby producing the larvicide (claim 9). Paldi teaches wherein said nucleic acid larvicide down-regulates a target gene selected from the group consisting of: (i) affecting larval survival; (ii) interfering with metamorphosis of larval stage to adulthood; (iii) affecting susceptibility of mosquito larvae to a larvicide; (iv) affecting susceptibility of an adult mosquito to an adulticide/insecticide; and (v) affecting fertility or fecundity of a male or female mosquito (claim 13), i.e. inhibit larval maturation and survival. Paldi further teaches that the dsRNA can be defined in terms of the nucleic acid sequence of the DNA encoding the target gene transcript, and it is understood that a dsRNA sequence corresponding to the coding sequence of a gene comprises an RNA complement of the gene's coding sequence, or other sequence of the gene which is transcribed into RNA [0141], such that the larvicide dsRNA can be delivered through a DNA construct or cassette encoding the RNAi [0169-0171]. Further rregarding claim 18 part (iii), Paldi teaches the method comprises administering the composition in yeast cells which comprises the nucleic acid larvicide [0173-0180]. Paldi teaches the RNAi of the invention targets multiple genes including sex-determining region sry gene AAEL000584 (Table 2B) as well as enzymes such as glutathione transferring genes including GST glutathione-s-transferase theta AAEL010500 (Table 2A).
However, Paldi does not teach the RNAi targeting of the gene AAEL017331.
GenBankGGT1 teaches that the gene LOC23687751 is also known as AAEL017331 and Gamma-glutamyl transpeptidase 1 (GGT-1), involved in the glutathione catabolic process in the Aedes aegypti mosquito species, known in the art before the effective filing date of the claimed invention.
Flavell teaches the gamma glutamyl transpeptidase gene (GGT1-1) is differentially expressed in SP (short photoperiod) of diapause in wasps (pg 38 para 2) and that RNAi targeting GGT1 alters the photoperiodic response in wasps (Fig 6.1). Flavell teaches In many species the control of diapause has been identified as being hormonally controlled and the physiological changes involved in diapause have been highly studied in a number of different models and non-model organisms where diapause is characterized by a cessation of organism development (pg 12 para 4). Flavell teaches there is a significant interaction observed between photoperiod (LP or SP) and condition (dsRNA-injected or control) in wasps which show a significant change in diapause when injected with dsRNA against GGT-1 (pg 72 para 1). Flavell teaches the knockdown of GGT-1 with dsRNA shows a significant change in the diapause of wasps (pg 74 para 2). Regarding the gamma glutamyl transpeptidase gene, Flavell teaches GGT is a membrane-bound protein that plays a key role in glutathione metabolism and has potential to influence signaling pathways such as catabolism of glutathione (normally an antioxidant) which results in low-level production of reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) and where superoxide diapause can be manifested as a reproductive or developmental arrest (pg 74 para 2).
However, the references do not provide sufficient teaching or motivation that targeting GGT1 in mosquitoes via a yeast-mediated RNAi would achieve larval lethality, given the lack of evidence in the art prior to filing regarding the GGT gene in mosquitos undermining the predictability of its knockdown within an effective insecticide composition. Applicants invention is an alternative iRNA composition targeting the at least one sex-linked larval lethal arthropod gene AAEL017331 (GGT). As such, it would have not have been obvious to apply the reference iRNA teachings to the sex-linked larval lethal arthropod gene AAEL017331 (GGT) in a mosquito species.
Response to Arguments
Regarding the §112b rejection of record of claim 18, Applicants have failed to remedy the lack of antecedent basis of “the yeast cell”, therefore the rejection is maintained.
Regarding the §103 rejection of record, Applicants argue (Remarks pg 5-7) that the references cited by the Examiner do not provide sufficient teaching or motivation that targeting GGT1 in mosquitoes via a yeast-mediated RNAi would be predictably effective. Applicants argue, specifically, that Paldi, Flavell, and GenBankGGT1 fail to provide a clear motivation for combining the reference teachings and that Flavell primarily addresses diapause and photoperiod effects in wasps, not mosquitos, at the pupae stage and does not teach or suggest the specific application of RNAi targeting GGT1 at the larval stage for mosquito control. Applicants further argue that Flavell demonstrates that injection of extracellular GGT leads to ovarian apoptosis, not larval lethality which is the desired outcome in mosquito sex separation and maturation control. Applicants argue the reference suggests that indiscriminate targeting of GGT could lead to non-selective effects, such as changes to production of reactive oxygen species (Flavell, p. 74-75) thus discouraging the skilled artisan from using this approach for selective sex- linked gene targeting in mosquitoes. Applicants argue that Flavell warns that knockdown of the GGT-1 gene will have no effect under certain conditions (LP) making the path taken by the claimed invention non-obvious.
Applicant’s arguments have been thoroughly reviewed and found persuasive to undermine the obviousness and predictability of an effective yeast delivered insecticide RNAi targeting the GGT gene in mosquitos, given Examiner’s response in the Allowable Subject Matter section above.
Conclusion
No claims are allowable.
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 extension fee 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 date of this final action.
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/JOHN CHARLES MCKILLOP/Examiner, Art Unit 1637
/EKATERINA POLIAKOVA-GEORGANTAS/Primary Examiner, Art Unit 1637