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 .
Claims 21, 25-43 are pending in the application.
This office action is in response to the amendment filed on 10/21/2025.
All previous rejection not reiterated in this office action are withdrawn.
Claim Rejections - 35 USC § 112
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 32, 35-37, 39 and 43 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.
Regarding claim 32, the recitation of “in which cells of the population of cells comprises DNA molecules” renders the claim indefinite because it is unclear what “DNA molecules” the claim is referring to. Does it mean the cells comprises their own DNA, or the source DNA? Is it in addition to the DNA mixture as recited in claim 21 or the mixture is inside the population of cells of the host species?
Regarding claims 35 and 36, the recitation of “a deterioration of products” renders the claim indefinite because it is unclear what products the claim encompasses, a biological species, a food source, a multicellular organism…?
Regarding claim 37, the recitation of “host species comprises a food source for the target species” renders the claim indefinite because it is unclear whether the host cells produces food for the target species, or host species is the food of the target species?
Regarding claim 39, the recitation of “selected from Lepidoptera, Noctuidae, or Pyralidae” renders the claim indefinite because when the member of a group is recited in alternative, it does not provide a list of member to be selected from.
Regarding claim 43, the recitation of “selected from a parasite and/or pathogen of skin, nail or of a mucous membrane” renders the claim indefinite because it is unclear whether the parasite is from skin, nail or mucous membrane, or only pathogen is from skin, nail or a mucous membrane. Further, the selection member recited in alternative “and/or” does not provide a list of member to be selected from.
Response to Arguments
Applicant states the language of claim 21 and 31 have been modified.
However, Applicant did not address the above rejection. Therefore, the rejection is still considered proper and thus maintained.
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.
Claim 21, 25-43 are 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 to inhibit growth of a target species by exposing said biological species to a mixture of DNA fragments from a source species and a host species, said source species being same as the target species, and said source species being selected from plants, fungi, insects, yeast, algae, nematodes and protozoa, the DNA fragment obtained by random fragmentation of extracted total DNA, or by random fragment synthesis starting from the total DNA, or the source species has a phylogenetic distance of less than 2 from the target species, does not reasonably provide enablement for such a method using a phylogenetically similar species, and for target species such as mammalian species including human. 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/use the invention commensurate in scope with these claims.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is "undue." These factors include, but are not limited to: (a) the nature of the invention; (b) the breadth of the claims; (c) the state of the prior art; (d) the amount of direction provided by the inventor; (e) the existence of working examples; (f) the relative skill of those in the art; (g) whether the quantity of experimentation needed to make or use the invention based on the content of the disclosure is "undue"; and (h) the level of predictability in the art (MPEP 2164.01 (a)).
The nature of the invention
The claimed invention is drawn to a method to inhibit a target species by exposing said target species to a mixture of DNA fragments from said a combination of source species and host species, wherein the source species is same as target species or a phylogenic species.
The breadth of the claims
The claimed method scope encompasses a method of inhibit growth in all biological species by exposing the species to DNA (intact or fragmented) from the same species and another different species, or other species that is considered to be phylogenetically similar.
The teaching from the specification and the presence of working example
The specification teaches inhibition tests demonstrated inhibitory effects by mixture of DNA obtained from BAC and YAC library of Arabidopsis thaliana, with mixture of DNA in BAC and YAC vector (experiment 1). The specification teaches microbial solutions of two libraries were sonicated and resulting cell homogenates were incubated under aerobic condition with Arabidopsis thaliana seedlings, and the seedling survival was lower in said solution compared to control, and with heterologous DNA only. Same results were observed with a genomic BAC library of Cyperus aesculentus, a fosmid library of C. elegans, a genomic BAC library of S. littoralis (experiment 2-5). Experiment 6 demonstrated that a yeast library comprising Drosophila DNA inhibits larvae fed. Experiment 7-9 demonstrates self-DNA integrated into chromosomal DNA is also able to inhibit the target species when fragmented. Experiment 10 demonstrates root growth is also inhibited by fragmented DNA from phylogenetically related species. However, the specification does not teach whether unfragmented total chromosomal DNA can inhibit the target species. Nor does the specification demonstrates target species other than plant, insect, microbial species, such as mammalian species or virus. The claimed scope is thus broader than the teaching from the specification.
The state of prior art and level of predictability in the art
The prior art (US 10,420,343) teaches microbial populations produce and secrete self-DNA molecules in form of different size fragments, which exert an inhibiting effect on the growth of said population (see page 7). The patent demonstrates inhibition of Acanthus Mollis, Lepdium sativum plants, Quercus ilex, Quercus pubescens, Hedra elix, ameplodesma…pinus halepensis, lens esculentum plants by exposure to self-DNA (see example 1-3). The patent also demonstrates inhibition of Aspergillus niger, Trichoderma harzianum fungi, Sarcophaga carnaria insect, Bacillus subtilis, Scenedesmus obliquus microalga, Physarium polycephalum protozoan by exposure to self-DNA (see example 4-9).
With regard to the term “phylogenetically similar,” the art teaches that “phylogenetic relationship” refers to the relative times in the past that species shared common ancestors. Two species are more closely related to one another than either one is to a third species if, and only if, they share a more recent common ancestor with one another than they do with the third species (see web page from Peabody museum of natural history, yale university 2008). The prior art recognize that a mushroom is phylogenetically closer to human than water lily. In the instant case, the claimed method encompasses inhibiting the growth of a target species with a phylogenetic similar species, which encompasses inhibiting the growth of mushroom with human DNA. The specification teaches “phylogenetically similar” means two species has a similar genome, however, there is no limiting definition with regard to the degree of similarity between two genome to meet the claim limitation. The teaching from example 10 is a specific example of phylogenetic angiosperms with phylogenetic distance between 0-26 (Figure 7), wherein only phylogenetic distance 2 or below exhibited inhibitory effect. In view of the limited teaching from specification, whether the target species may be inhibited by DNA from a phylogenetically similar (interpreted based on BRI in view of the specification) species is unpredictable.
With regard to the biological species mammalian species, or acari and viruses, the specification does not provide any evidence that the growth of said biological species may be inhibited by exposing to random fragmented self-DNA. Target species from mammalian cells, virus or acari differ significantly from the biological species that was described in the specification of which inhibitory effect from self-DNA is observed, especially viruses. Unlike other recited biological species, the growth of virus is not self-reliant but relies on the host cell machinery. There has not been an observation that random fragments of any type of viral DNA may inhibit its growth or replication. As such, whether self-DNA from mammalian cell, acari and viruses may inhibits its growth is unpredictable.
The amount of experimentation needed
In summary, the claimed method is described in the specification as using fragmented self-DNA inserted into BAC, YAC vector or chromosomal DNA, or phylogenetically related DNA with phylogenetical distance less than 2, for inhibiting growth in some plants, fungi, insects, microalgae and protozoa. However, the specification does not teach unfragmented total DNA that comprises self-DNA, or DNA from species with phylogenetic distance of more than 2 can also be used to perform the claimed method. The specification also fails teach the full scope of the biological species the inhibitory effect is observed. Based on the limited teaching from the specification and unpredictability exists in the prior art, the claimed invention is only enabled to the scope as indicated above.
Response to Arguments
Applicant states that the amendment to claim 21 is in line with the indication in the previous office action that is indicated in the enabled scope.
This statement is only partially correct because the enabled scope is directed to fragmented DNA from source species, which does not include total chromosomal/genomic DNA, or other DNA of large size. For reason discussed in previous office action and set forth above, this rejection is still considered proper and thus maintained.
Claim Rejections - 35 USC § 103
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 (i.e., changing from AIA to pre-AIA ) 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.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 21, 25-27, 29-38, 40-43 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mazzoleni (WO2014/020624) hereafter as Mazzolini 1, in view of Mazzoleni (New Phytologist 2015, IDS), hereafter as Mazzolini 2. This is a new ground of rejection necessitated by amendment.
Claim 21 is drawn to a method of inhibiting a target species that comprises a single step of exposing said target species to a mixture of DNA molecules comprising source species and host species.
Mazzolini 1 teaches a method of for inhibiting a target species by exposing the target species to a mixture of total DNA fragments, wherein the total DNA fragments is randomly fragmented for the prevention and treatment against at least one pathogenic, parasitic, or infesting species of the plants or environment, wherein the total DNA is total DNA of said pathogenic, parasitic or infesting species, and/or at least one phylogenetically similar species (page 12, lines 22-29). The DNA mixture taught by Mazzolini that comprises DNA from pathogenic, parasitic or infesting species, and at least one phylogenetically similar species is intended for use as biocide, herbicide, fungicide, insecticide, antiprotozoic, algaecide and bactericide (page 14, lines 1-3). Mazzolini’s teaching also contemplates the application of said DNA fragments mixture to soil, resulting in durable application in both environmental and economic benefits (page 19, liens 12-15).
Mazzoleni 1 does not specifically teach exposing a target specie to two different species, one of them being the target species, and the other being a different species.
Mazzoleni 2 teaches the studying the inhibitory effect of decomposed litter, wherein DNA accumulation in litter and soil was measured and DNA toxicity was assessed (summary). Mazzoleni 2 teaches litter autotoxicity is related to exposure to fragmented self-DNA (Figure 2 and legend, Figure 6 and legend). Mazzoleni 2 teaches “it has to be noted that the total DNA found in both litter and soil system derived from both decomposing plant tissues and from microbial turnover.”
It would have been obvious to an ordinary skilled in the art that when applying the fragmented DNA mixture of source species or phylogenetically similar species to the target species through a medium such as soil or litter as taught by Mazzoleni 1, it would contain a mixture of DNA from different species including microbial and plant DNA as taught by Mazzoleni 2. Since the specification does not give a limiting definition for “host species,” the microbial DNA naturally present in the environment meets this limitation because they are different from the plant DNA, for example. Therefore, the claimed method of claim 21 would have been obvious to an ordinary skilled in the art at the time the application was filed.
Regarding claim 25, Mazzolini teaches total DNA from the pathogenic, parasitic or infesting species (p12, line 21-27), which meets the limitation of chromosomal DNA.
Regarding claim 26, Mazzolini teaches one embodiment in which the nucleic acid fragments can be engineered in vectors (page 14, line 11-12). Since vector sequences are not from the pathogenic, parasitic or infesting species, the DNA composition thus comprises chimeric DNA molecules as claimed.
Regarding claim 27, it depends on claim 26, so that the limitation of DNA sequences being genomic chromosomal DNA is from host species is alternative to artificial DNA sequences from an artificial DNA construct. This claim is rejected for same reason as applied to claim 26.
Regarding claim 29, since Mazzolini teaches fragmented DNA from source species, the vector that comprises said fragmented DNA meets the limitation of partial DNA sequences of chromosomal DNA.
Regarding claim 30 and 31, since the specification does not provide a limiting definition for “phylogenetically similar species,” it would have been inherent that are at least from same family.
Regarding claims 32 and 34, it would have been obvious to an ordinary skilled in the art soils or litter in nature would comprise microbials, which are cells that comprise DNA molecules.
Regarding claim 33, the DNA composition taught by Mazzolini is fragmented (page 12, lines 22-29).
Regarding claims 35 and 36, Mazzolini teaches the DNA is from pathogenic, parasitic species (page 12, line 24), which meets the limitation of a disease associated species, and infesting species.
Regarding claim 37, it is well known in the art that many soil microbial species provide food for plants through nutrient transformation, organic matter decomposition and symbiotic relationships. It would have been obvious to an ordinary skilled in the art that applying self-DNA through soil in nature would comprise such soil microbial species that comprise food source for target species such as plant.
Regarding claim 38, the plant and microbial species in soil or litter are phylogenetically distant.
Regarding claim 40, Mazzolini teaches the composition may be formulated in suspension, wettable or soluble powders, emulsions in water…or other pharmaceutical compounds (page 15, lines 1-12), which meets the limitation of pharmaceutical acceptable form.
Regarding claim 41, Mazzolini teaches the composition may be biocide, herbicide, fungicide… (page 13-14, bridging paragraph), which meets the limitation of agronomical composition.
Regarding claim 42, Mazzolini teaches the composition being fungicide, bactericide, and can be administered to said pathogenic parasitic species by surface contacting, cytotropic administration, systemic administration including injection, inhalation (page 14, lines 1-5).
Regarding claim 43, Mazzolini teaches the target species may be a parasitic species of a man or an animal (page 14, line 24-27).
Claim(s) 28 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mazzolini 1 and Mazzoleni 2, as applied to claims 21 and 26, in view further view of Ma (Gene, 1992, Vol.117, pages 161-167).
The teaching from Mazzolini has been discussed above. However, Mazzolini does not teach the chimeric DNA comprises non-source species DNA from artificial DNA sequences (claim 28), or phylogenetically distant species.
Ma teaches vectors for plant transformation and cosmid libraries (title). Ma teaches construction of vectors for transforming into plant genomes such as pCIT20, and pCIT30 (Figure 1 and legend). Ma teaches pCIT30 is used for generation of plant library from Arabidopsis thaliana plant (page 164-165, bridging paragraph).
It would have been obvious to an ordinary skilled in the art that the plant DNA may be cloned into artificially constructed vector based on the teaching from Mazzoleni and Ma. The ordinary skilled in the art reading Mazzolini, who teaches that the fragmented DNA may be inserted into vectors, would recognize that synthetic vector such as pCIT30, a cosmid, may be used to clone fragmented plant DNA as suggested by Mazzolini. The ordinary skilled in the art would have reasonable expectation of success to inserted fragmented plant DNA into artificially constructed vectors following combined teaching from Mazzolini and Ma. Therefore, the claimed invention of claim 28 would have been prima facie obvious to an ordinary skilled in the art at the time the application was filed.
Claim(s) 39 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mazzolini 1 and Mazzoleni 2, as applied to claim 21, in further view of Montezano et al (African Entomology 26 (2), pages 286-300, 2018).
The teaching from Mazzolini 1 and Mazzoleni 2 has been discussed above. However, Mazzolini does not specifically mention the pathogenic, parasitic species is from Lepidoptera, Nocutuidae.
Montezano teaches the fall army worm (Lepidoptera: Noctuidae) is the most important notuid pest in Americas and has become invasive pest in Africa (abstract). Montezano teaches Spodoptera frugiperda larvae attack a large number of cultivated plant species, with severe damage to maize, sorghum, and other monoculture crops such as cotton and soybean (page 286-287, bridging paragraph).
It would have been obvious to an ordinary skilled in the art the method of inhibiting target species taught by Mazzolini may be used to control Lepidoptera noctuidae, an invasive pest to many useful agricultural products as taught by Montezano. Since Mazzolini already demonstrated inhibiting target species in various organism including, plant, microbial organism and insect, the ordinary skilled in the art would have reasonable expectation of success to isolate DNA from said insect, fragmenting DNA, and treating the plants with said DNA to reduce the invasion from said insect. Therefore, the claimed invention of claim 39 would have been prima facie obvious to an ordinary skilled in the art at the time the application was filed.
Response to Arguments
Applicant asserts that the teaching from Mazzoleni does not teach every limitation of amended claim 21.
This argument has been considered and the 102 rejection is withdrawn, and replaced with the 103 rejection as discussed above.
Conclusion
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.
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/CELINE X QIAN/ Primary Examiner, Art Unit 1637