17DETAILED 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 .
Priority
Applicant’s claim to priority from PCT/US2019/058910 filed 10/30/2019 and provisional application No. 62/752,880 filed 10/30/2018 is hereby acknowledged.
Application Status
This application is a national stage entry under U.S.C. § 371 of PCT/US2019/058910 filed 10/30/2019.
Amendments to claims filed 12/23/2025 are hereby acknowledged. Claims 1-3, 5, 9-18, 20-23, 28, and 30-46 are cancelled. Claims 6-8, 19, 47-55 and 57-58 are currently amended. Claims 4, 6-8, 19, 24-27, 29 and 47-58 are pending.
Claims 24-27, and 29 are withdrawn from consideration as drawn to non-elected invention.
Therefore, claims 4, 6-8, 19 and 47-58 are currently under examination in this office action.
Any objection or rejection not reiterated herein has been overcome by Applicant’s amendments and is withdrawn. 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.
Claim Objections
Claim 58 is objected to because of the following informality: the claim recites “wherein the one or more species of double stranded RNA comprises a sequence transcribable from a double stranded DNA template amplicon formed amplification of a primer pair…”. The claim should recite “wherein the one or more species of double stranded RNA comprises a sequence transcribable from a double stranded DNA template amplicon formed after amplification using of a primer pair…”. Or the claim can recite the term “by” in replacement of the term “after”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(d)
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.
Claims 47-55 are 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.
Regarding claims 47-55, they each recite a portion of claim 4. They do not further limit the subject matter already recited in claim 4, and they do not include all the elements of the claim from which they depend.
Applicant may cancel the claims, amend the claims to place the claims in proper dependent form, rewrite the claims in independent form, or present a sufficient showing that the dependent claims complies with the statutory requirements.
Claim Rejections - 35 USC § 112(a)
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.
Claims 4, 6-8, 19 and 47-57 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.
MPEP 2163.II.A.3.(a).i) states, “Whether the specification shows that applicant was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention”.
For claims drawn to a genus, MPEP § 2163 states the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
Nature of the Invention:
Claim 4 is drawn to “A composition comprising an effective amount of
a compound or compounds that reduce(s), inhibit(s), or prevent(s) expression or activity of an eggshell formation, melanization, and/or crosslinking pathway comprising a mosquito Eggshell Organizing Factor 1 (EOF1) protein and optionally one or more proteins selected from Nasrat, Closca, Polehole, Nudel, CATL3, DCE2, DCE4, and DCE5, wherein the compound or compounds reduce(s), inhibit(s), or prevent(s) expression or activity of one or more mosquito target genes selected from the group consisting of EOF1, Nasrat, Closca, Polehole, Nudel, CATL3, DCE2, DCE4, and DCE5, or gene products thereof”.
Claims 6-8 are drawn to “one or more functional nucleic acids or vectors encoding functional nucleic acids”, and “wherein the functional nucleic acids are selected from the group consisting of antisense molecules, siRNA, miRNA, ribozymes, RNAi, and external guide sequences” that can target any one of the mRNAs that are encoded by nucleic acid of SEQ ID NOs 191-199, 201, 220-231, 233-247.
Claim 19 is drawn to a composition “wherein the compound is a protease inhibitor”, optionally a protein, a peptide or a small molecule.
Claims 56 and 57 are drawn to a composition “wherein the compound is a gene editing composition or a vector encoding a gene editing composition” and “wherein the gene editing composition is selected from a CRISPR/Cas system, Zinc Figure (sic) Nucleases, Transcription Activator-Like Effector Nucleases, or triplex forming molecules.”
It is therefore expected in the instant Application a disclosure of the names of specific compounds capable of reducing, inhibiting or preventing the expression or activities of the specific named genes, i.e., EOF1, Nasrat, Closca, Polehole, Nudel, CATL3, DCE2-5 and examples of formulations showing the most effectiveness on the genes’ expression or activities. It is expected in the disclosure an example and reduction to practice of an effective amount of a compound, as well as the structure of said compounds.
Applicant claims compounds that are nucleic acids or vectors encoding the nucleic acids, therefore it is expected in the disclosure a reduction to practice with specific structures, i.e. enumeration of residues, conserved sequences and motifs necessary, responsible for, and capable of reducing, inhibiting or preventing the EOF1, Nasrat, Closca, Polehole, Nudel, CATL3, DCE2-5 genes expression and/or their genes and/or protein activities.
Applicant claims compounds that can be a gene editing composition. It is therefore expected a reduction to practice, an example showing a CRISPR/Cas system with a specific Cas protein effector, e.g. Cas9, Cas12 or isoforms, or variants in recombinant fusion proteins that are most effective at avoiding off-target effects, with specific enumeration of residues for guide RNAs, so that a person with ordinary skills in the art could reproduce the effect of the composition with “an effective amount of the said compound”. Applicant claims Zinc Finger nucleases, TALENs or triplex forming molecules; it is therefore expected at least one example of such compound.
Applicant claims compounds that can be protease inhibitors, proteins, peptides or small molecules; it is therefore expected a reduction to practice showing examples of a compound or mixture of compounds capable of reducing, inhibiting or preventing the genes expressions or activities.
The State of the Art:
Functional Nucleic Acids, e.g. “antisense molecules, siRNA, miRNA,
ribozymes, RNAi, and external guide sequences”:
Zhu ( Zhu,K.Y. et al. “Mechanisms, applications, and challenges of insect RNA
interference”. Annual Review of Entomology, Vol. 65 (2020), pp: 293-311) teaches that there is compelling evidence to support the role for RNA interference (RNAi) in antiviral immunity in insects (see “Abstract” and page 294, “Introduction”, first paragraph). It has been hypothesized that RNAi is highly variable or inefficient in insects other than coleopterans, and that RNAi efficiency among insects is correlated with the prevalence of viral infections in them (see “Abstract” and page 294, “Introduction”, first paragraph).
Zhu also teaches that there are three mains pathways for RNA interference (RNAi) in insects, involving siRNAs, miRNAs, piRNAs (see page 294 and Figure 1). Therefore, the structure of the antisense molecules may affect the pathway used inside the cells. Zhu also teaches that the stability of the interfering RNA highly depends upon the type of insects, since insects have significant differences in nuclease activity (see page 299, last paragraph).
Vogel (Vogel, E. et al. “RNA interference in insects: protecting beneficials and controlling pests”. Frontiers in Physiology, Vol. 9 (2019), p: 1912) teaches that insects have an interesting aspect of RNAi response known as systemic RNAi (sysRNAi ) in which administration of dsRNA can result in the generation of an RNAi response throughout the entire body (page 2, left column, third paragraph). Vogel teaches that this response is due to cellular uptake mechanisms relying either on scavenger receptors in cells or lipophorins in hemolymph. Vogel teaches that these proteins have a role in protection, transport or both, of the dsRNA throughout the body (page 2, left column, third paragraph). However, the uptake of naked dsRNA seems to be length dependent. It occurs efficiently for long dsRNA molecules of around 20-500 base pairs (bp) or even 1000 bp. Vogel also teaches that for smaller molecules such as siRNA, this efficiency decreases (see page 2, left column, third paragraph).
Therefore, the size of the molecule, if “naked” is of importance for its transport and RNA interference response.
Vogel also teaches that the efficiency of the RNAi response may vary between species and even within the same organism (see page 3, left column, “Variable efficiency of the RNAi response” section). Vogel also teaches a limiting effect due to nucleases, not only in digestive tract but also in hemolymph (see page 4, left column, third paragraph). Vogel teaches that the RNAi response is tissue-dependent and there are intra-species differences in sensitivity and resistance (see page 4, right column).
Vogel teaches target selection and construct design (see page 5, “Target selection and construct design” section, left and right columns). Vogel points out that off-target effect should always be considered, therefore dsRNA constructs should preferably be chosen in non-conserved regions of the target mRNA to avoid cross-silencing among other species or isoforms of the gene of interest. Vogel teaches that species-specific RNAi can be obtained if dsRNA construct is well designed (see page 5, “Target selection and construct design” section, right column).
Vogel also teaches that viral delivery systems show a lot of potential and are generally considered to be among the most efficient methods for dsRNA delivery; nanoparticles, liposomes and proteinaceous delivery systems are also to be considered, as well as chemical modifications of the dsRNA (see pages 5, 7-8, “RNA delivery systems” section).
Therefore, according to Vogel, a composition comprising dsRNA to be effective needs to be well-designed, requiring further specification on content as far as the primary structure (i.e. base sequence and length, specific target sequence within the gene target), and on the delivery method.
Lam (Lam, J.K.W. et al. “siRNA versus miRNA as therapeutics for gene silencing”. Molecular Therapy—Nucleic Acids, vol. 4 (2015), P: e252) teaches gene silencing mechanisms of siRNA and miRNA (see title and abstract). Lam teaches that miRNAs are produced in a cell following post-transcriptional processing. First the primary miRNA transcript (pri-miRNA) produces a 70-100 nucleotide precursor (pre-miRNA). The pre-miRNA precursors are then processed by Dicer into a 18-25-mer miRNA duplex which associates with RISC and binds to the target mRNA through partial complementary base pairing with the consequence that the target gene silencing occurs via translational repression, degradation, and/or cleavage (see Table 1 and page 2, right column). Lam also teaches that, in contrast, siRNA must be fully complementary to its target mRNA (see page 2, right column, last paragraph) (see Figure 1).
Lam further teaches that the RNA duplex needs to be carefully designed to warrant correct guide strand selection by RISC. Two major sequence parameters are known to determine the guide strand selection: (i) the asymmetry rule and (ii) 5’ nucleotide preference; both of which can be applied to duplex RNA design (see page 5, left column, “Strand selection” section). Lam teaches in Table 3 a summary of commonly employed strategies to enhance the efficacy and specificity of siRNAs, and to reduce the off-target effects.
Therefore, to obtain an effective compound, i.e. a dsRNA for RNAi, one can apply the asymmetry rule, utilize a 5’ nucleotide preference, manipulate the G/C content, avoid sequences similar to miRNAs present naturally and avoid immunostimulatory motifs. Those modifications in primary sequence can lead to an enumeration of residues different from those in a direct complementary strand of target mRNA.
Bryant (Bryant, B. et al. Proceedings of the National Academy of Sciences USA, Vol.107 (2010), pp: 22391-22398; previously cited) teaches a composition comprising a compound effective in reducing the activity of an important component of egg development pathway in a mosquito (see title and abstract). Bryant teaches that miR-275 plays an important role during vitellogenesis (see page 22392, “[R]esults” section, left column, lines 15-16). Bryant teaches a composition comprising a compound reducing miR-275 expression, miR275-antagomir (mir-275-ant) (see Figure 3). Bryant teaches that antagomir depletion of miR-275, with mir-275-ant, does affect drastically egg development (see page 22394, left column, lines 30-34 and right column, lines 28-29 and figure 5).
Bryant teaches a compound comprising a functional nucleic acid, that is an antisense molecule, mir-275-ant (see Figure 3).
Bryant give specific sequence to amplify the nucleotide sequence corresponding to the dsRNA and provides direction for cloning in plasmids and expression (see page 22397, “RNA interference” section). Bryant also provides specific pattern of chemical modifications applied to the antagomir (see sequence and pattern in “synthesis and application of antagomirs” section, page 22397).
Huang (Huang, Y-J. S. et al. “Biological control strategies for mosquito vectors of arboviruses”. Insects, Vol. 8 (2017), p: 21) teaches the use of ribozymes, but only to target the viruses borne by the mosquito vector and introduce resistance to the viruses (see title, abstract, and page 12, last paragraph, section 4.1). The engineered hammerhead ribozymes were designed to target the genomic RNA of DENV-2 (Dengue virus gene). There is no example of using a ribozyme targeting the insect vector genes.
Therefore, one with ordinary skills in the art would need more information identifying specific region in an insect target gene to obtain an effective amount of ribozymes to reduce, inhibit or prevent gene expression.
Gene editing composition: “Functional Nucleic acids”,” external guide
Sequences” or vectors encoding the functional nucleic acids and/or the gene editing composition.
Hammond (Hammond, A. et al. Nature Biotechnology, Vol.34 (2016), pp: 78-83; previously cited), as evidenced by LeMosy (LeMosy, E.K. et al. Developmental Biology, Vol. 217 (2000), pp: 352-361; previously cited) teaches the introduction of a composition comprising CRISPR-Cas system (see figure 1a) in a mosquito, as a method to inhibit the mosquito female reproduction, targeting both AGAP005958 gene , an ortholog of yellow-g protein in Drosophila and AGAP007280 gene , an ortholog of Drosophila’s Nudel gene (see page 79, left column, lines 20-30 and 32-35; and Table 1 and figure 1).
These genes are known to be important for egg-laying and egg hatching (see figure 1c). Yellow gene is known to be important in regulating the production of melanin pigment (melanization) in the eggs and Nudel is known as a protease necessary in ventral polarity in egg formation pathway (as evidenced by LeMosy, see title).
Hammond teaches that the composition is effective in reducing the level of egg formation and the number of hatched larvae (see figure 1c). Hammond teaches a composition that comprises guide RNAs targeting AGAP005958 or AGAP007280 gene and a plasmid-based source of CAS9 (see figure 1). The composition taught by Hammond comprises guide RNAs, i.e. “external guide sequences”.
Hammond provides specific information for constructs and sequences of primers and guide sequences ( see page 84, “Online Methods”, “Generation of donor constructs for gene targeting by CRISPR or TALEN-mediated HDR” section, and “Generation of CRISPR and TALEN constructs”.
3) Protease inhibitors, proteins, peptides, or small molecules:
Hammond: The gene editing composition taught by Hammond comprises an
inhibitor of Nudel ortholog; Nudel and its ortholog are proteases as evidenced by LeMosy (see title). Therefore, inherently, the compound is a protease inhibitor.
What the Specification does and does not teach:
-1) The Specification presents a “Summary of the invention” as comprising
“compositions and methods for reducing or preventing mosquito embryos from completing embryogenesis and/or reaching the first larval instar, reducing, delaying, or otherwise disrupting eggshell formation and/or egg melanization, reducing egg survival, altering the follicular shape of eggs, increasing permeability of oocytes to water, reducing female fecundity, increasing an embryonic lethal phenotype, or any combination thereof are provided.”
-2) The Specification presents a “Brief description of the drawings” comprising Figures 1A-D, 2A-O, 3A-C, 4A-B, 5A-D, 6A-D, 7A-D, 8A-D, 9A-B, 10 and 11.
-Figures1A-D present schematic diagram of experimental time course for a dsRNA microinjection and bar graphs representations of effects of dsRNA (RNAi of EOF1 gene) on number of eggs laid and viability. The composition used is not disclosed, no teaching about the dsRNA specific sequence and nucleotide modifications, base or internucleotide linkage modifications; there is no carrier or vehicle disclosed.
-Figures 2A-O present schematic diagram of experimental time course for dsRNA microinjection (RNAi of EOF1 gene), blood feeding, oviposition and female fecundity. As in Fig.1, the specifics of the composition used are not disclosed.
-Figures 3A-C present tissue-specific and developmental expression pattern of EOF1 in Aedes aegypti mosquitoes. Multiple tissue expressions are shown, especially in ovaries where there is also a RNAi experiment knocking down EOF1 transcripts in ovaries. As in Fig.1 and 2, the specifics of the composition used are not disclosed.
-Figures 4A-B present data using RNAi of EOF1 in a different species of mosquitoes, Aedes albopictus. As previously, effects of microinjections of antisense RNA are measured as effect on female fecundity by counting number of eggs laid and their viability. No disclosure of a specific composition teaching an enumeration of base sequence for the antisense RNA, no modification is taught, no disclosure about the carrier or vehicle.
-Figures 5A-D also present data of a time course effect of dsRNA microinjection in Aedes aegypti mosquitoes, counting eggs number, percentage of melanization of the eggs and viability. There is no disclosure of a specific composition as previously mentioned.
-Figures 6A-D present tissue-specific developmental expression pattern of Nasrat, Closca, Polehole,and Nudel genes. Expression levels are normalized to S7 ribosomal protein transcripts levels in the same cDNA samples. Expression data are collected from different cohorts of mosquitoes. There is no correlation between this set of data and the composition claimed.
-Figures 7A-D present data and effects of dsRNA microinjections using different genes (Nasrat, Closca, Polehole and Nudel) on eggs counts, melanization and viability. There is no disclosure of a specific composition and enumeration of base sequence, modifications for RNA stability and carriers for each gene knock-down.
-Figures 8A-D present data and effects of dsRNA microinjection knocking-down Nudel gene expression on oviposition, eggs counts, melanization and viability of said eggs. As before, there is no disclosure on the specifics of the antisense RNA used.
-Figures 9A-B present data obtained in vitro on egg melanization assays, percentage of melanization obtained after knocking down Nasrat, Closca, Polehole and Nudel gene expressions. There is no disclosure of a specific antisense construct.
-Figure 10 shows eggshell peptide abundance changes in response to knocking down EOF1 gene expression via proteomic analysis. There is no disclosed sequence or modification of antisense, no specifics on the composition used.
-Figure 11 present a biological model for involvement of specific proteins during eggshell formation and melanization in Aedes aegypti mosquitoes. There is no mention of compositions used to arrive at the model.
- 3) The Specification also teaches a “Detailed description of the invention” in which there are generic definitions for terminology used, compositions, exemplary EOF1 genes and gene products, examples of other target genes and gene products (with Full-length base sequences of examples of genes with GENBANK Accession numbers, see Tables 1 and 5, and SEQ ID NOs; see pages 21-42), inhibitors of target genes/gene products with a listing of functional nucleic acids (antisense, ribozymes, external guide sequences, RNA interference), gene editing compositions (strand break inducing elements such as CRISPR/Cas, Zinc Finger Nucleases, Transcription Activator-Like Effector Nucleases), comprising gene altering polynucleotides, triplex-forming oligonucleotides, with a recitation of oligonucleotide composition such as heterocyclic bases, sugar modifications, internucleotide linkages, and protease inhibitors, as they would be taught in generic reviews of the art.
This section also has a “Methods of use” largely documented with prior art references on the techniques, the methods of inhibiting target genes/gene products in mosquitoes, pesticide compositions and methods of administration. This section also recites diseases to be treated and mosquitoes to be targeted, kits, methods for screening for mosquito-specific genes, target identification in silico, validation of said targets, screens for enzymes inhibitors.
On page 81 of the disclosure, Applicant discloses “Examples” in which the experiments with data shown in the Figures are presented in details.
Although Applicant presents a large body of experimentation for studying the mosquito tissues, eggs, developmental stages and different genes expressions in these stages, Applicant does not disclose sequences beyond those used as primers to amplify the specific sequences chosen (see pages 94-95, Tables 2, 3, 4 and 6).
Conclusion:
Taking into consideration the factors outlined above, including the nature of the
invention, the state of the art, the guidance provided by the applicant and the specific examples, it is the conclusion that Applicant does not possess the invention, i.e. a specific compound disclosed with a specific enumeration in sequences for functional nucleic acids, comprising a specific modification pattern, within a specific formulation (i.e. carrier, vehicle, or excipient) or a specific protease or enzyme inhibitors provided with effective concentrations within a specific formulation (i.e. mix of compounds within a diluent or excipient), capable of reducing, inhibiting, or preventing the expression or activities of EOF1, Nasrat, Closca, Polehole, Nudel, CATL3, or DCE2-5 genes. There is no specific written example of a structure of an inhibitor within the Specification that would lead one with ordinary skills in the art to a different conclusion.
Response to Arguments
Applicant's arguments filed 12/23/2025 have been fully considered but they are not persuasive.
Regarding Applicant statement that “the examiner has the initial burden, after a thorough reading and evaluation of the content of the application, of presenting evidence or reasons why a person skilled in the art would not recognize the written description of the invention as providing adequate support for the claimed invention” MPEP §2163 II”, Examiner would like to remind that the claims, as written, encompass any compound that likely would have an effect on the eggshell formation, melanization, and/or crosslinking pathways. A presentation of an effective amount of any compound is not given in the Specification, except for a 2 µg of sdRNA (see Specification, page 82, line 6).
While claiming a potentially broad genus of compounds, Applicant only gives details for only one species of compounds, i.e., dsRNA used in RNA interference, as a reduction to practice.
Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
However, since the claims are broad, a reduction into practice is actually necessary to be able to determine whether the claimed elements have solid support in the Specification, and do not encompass limitations that are already claimed and potentially patented elsewhere.
Regarding the Protease inhibitor cocktail referred to on page 20 of Remarks, it was expected a single compound or mix of compounds that are novel and patentable as a new claimed composition. The “Complete™ Mini, EDTA-free Protease inhibitor Cocktail” from Roche, is known as a reagent that is used routinely. Examiner interprets the use of this cocktail inhibitor as a “security blanket” to prevent degradation of proteins necessary for the making, and the transporting of nucleic acids, when dealing with whole cells and/or extracts comprising proteases, most likely to interfere with a PCR reaction, and/or to make sure that the protein deficiencies observed are the result of specific gene expression interference, RNAi knockdown, and not a direct effect of endogenous proteases-induced protein degradation (see pages 95-99).
The use of the protease inhibitor cocktail to inhibit melanization of wild-type mature follicles as described in the paragraph starting line 31 of page 99, was perceived as a proof-of-concept for the effect of a general cocktail comprising a mix of undescribed protease inhibitors, in favor of the theory that specific targeted inhibition could have effect. However, when considering Figure 9B, it is clear that the number of eggs melanized after applying the protease inhibitor cocktail for 10 minutes or 20 minutes is not different from the melanized untreated eggs number. An effect is shown only at 0 minute, i.e. upon immediate treatment with the protease inhibitor cocktail at dissection. Therefore, it is not clear whether it is the treatment or whether it is the dissection that actually inhibits melanization at this time point.
Even in the case of a direct effect of the cocktail, Examiner does not interpret the use of this cocktail as a specific and targeted inhibition of expression of EOF1, or any other proteins involved in the targeted pathways. No specific inhibitor is presented in practice. No evidence of effect on expression of a gene is shown.
Therefore, the rejections are maintained.
Allowable Subject Matter
Claim 58 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
No Claim is allowed.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.
Any inquiry concerning this communication or earlier communications from the
examiner should be directed to ALEXANDRA G DACE DENITO whose telephone number is (703)756-4752. The examiner can normally be reached Monday-Friday, 8:30-5:00EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil Hammell can be reached at 571-270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/A.D./Examiner, Art Unit 1636
/NANCY J LEITH/Primary Examiner, Art Unit 1636