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 .
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.
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 February 23, 2026 has been entered.
The amendment filed February 23, 2026 has been entered. Claims 1, 8-9, 12-13, and 37 were amended, claims 2-4, 7, 10-11, 15-17, 21-32, 35-36, and 38-58 are canceled, and claims 62-63 are added.
Applicant’s arguments filed February 23, 2026 were fully considered but they were not persuasive. Rejections and response to arguments as they currently apply are addressed below.
This application is a 371 of PCT/US2020/049457 filed September 4, 2020 and claims benefit of provisional application 62/896,944 filed September 6, 2019.
Claims 1, 5-6, 8-9, 12-14, 18-20, 33-34, 37 and 59-63 are pending in this application.
Claim Interpretation
With respect to instant claim 12, which recites, “wherein the insect pollinators are administered the composition in the same area treated with the pesticide”. The claim is interpreted to include wherein the same area encompasses administration to the pollinator itself.
With respect to instant claim 37, which is directed to a pharmaceutical composition and recites the phrases “for prophylactic administration” and “to protect against impairment of a cognitive function of the insect pollinator”. The Examiner notes that it is well settled that “intended use” of a composition or product, e.g., “for prophylactic administration”, “to protect against impairment”, will not further limit claims drawn to a composition, so long as the prior art discloses the same composition comprising the same ingredients in an effective amount, as the instantly claimed (See MPEP 2111.02 (II)).
Claim Objections
Claim 6 is objected to because of the following informalities:
In claim 6 the phrase “3-O-Rhamnoside” should read “3-O-rhamnoside”.
Appropriate correction is required.
Specification
The disclosure is objected to because of the following informalities:
Throughout the specification, the term “Rhamnoside” should not be capitalized (pg. 3, line 33, pg. 19, line 19).
In the table on page 23 of the specification, the phrase “Quercetin3-O-rhamnoside” should read “Quercetin 3-O-rhamnoside”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112 (b)
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 12-13 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 claims 12-13: Claim 12 recites inter alia, “wherein the insect pollinators are administered the composition in the same area treated with the pesticide.” Claim 13 recites inter alia, “wherein the insect pollinators are administered the composition in an area separate from the pesticide.” It is unclear what the boundaries are in determining what constitutes the “same” or “separate” areas. The instant specification provides no definition of these terms. For example, if the pollinator is administered the composition mere inches away from a pesticide, does that constitute a same area or separate area? If a pesticide is applied over a wide area, and the composition is placed within or adjacent to, does this constitute the same area or a separate area? In short, the claims include relative terms which a person of ordinary skill would be unable to ascertain the metes and bounds of and are thus rendered indefinite (See MPEP 2173.05(b)).
Regarding claim 12: Claim 12 recites inter alia, “wherein the insect pollinators are administered the composition in the same area treated with the pesticide.”. The phrase “same area treated with the pesticide.” renders the claim indefinite because it conflicts with earlier claim 9, of which claim 12 depends from, which limits exposure to pesticide to “by treating an area”. The phrase “treated” in claim 12 implies that the area has already been treated. It is unclear whether the claim is stating administration is occurring after the area is treated with a pesticide, which conflicts with claims it depends from. Thus the phrase leads to a lack of clarity in the claim thereby rendering it indefinite.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 37 and 61 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wong (PLoS One, 2018, IDS filed August 10, 2023).
Regarding claims 37 and 61: Wong teaches treatment of honey bees exposed to 0, 15, 45, 75, 105, and 135 ppb imidacloprid with 0.25 mM quercetin or 0.5 mM p-coumaric acid in a sucrose water diet (i.e. sucrose is a carbohydrate, artificially feed supplement for ingestion, pg. 5, para. 1). The diet solutions were prepared freshly for use in both short-term and long-term longevity assays (pg. 4, para. 3). According to the instant specification 200 µM (i.e. 0.2 mM) p-coumaric acid is effective to protect against cognitive impairment (pg. 73, lines 3-4, pg. 75, lines 27-31). Wherein the composition of Wong includes 0 pesticide concentration and comprises effective amount of p-coumaric acid and can be administered it can necessarily protects against impairment of a cognitive function of an insect pollinator and is suitable for prophylactic administration, absent evidence to the contrary.
Claim Rejections - 35 USC § 103
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.
Claims 1, 5-6, and 61-63 are rejected under 35 U.S.C. 103 as being unpatentable Wong (PLoS One, 2018, IDS filed August 10, 2023) as applied to claims 31 and 61 above as evidenced by Williamson (J. Experimental Biology, 2013, IDS filed August 10, 2023) and National Pesticide Information Center (Imidacloprid, 2018 cited in previous action).
Regarding claims 1, 5-6, and 61-63: Wong teaches certain phytochemicals, including quercetin and p-coumaric acid, are ubiquitous in the honey bee diet and are known to upregulate cytochrome P450 genes encoding enzymes that detoxify insecticides (abstract). Wong teaches treatment of honey bees exposed to 15, 45, 75, 105, and 135 ppb imidacloprid with 0.25 mM quercetin or 0.5 mM p-coumaric acid in a sucrose water diet (i.e. sucrose is a carbohydrate, pg. 5, para. 1). The amount of imidacloprid was chosen to mimic concentrations encountered by bees under field conditions (pg. 5, para. 1). Wong teaches that amelioration of pesticide toxicity by p-coumaric acid and quercetin is due to the induction of CYP9Q enzymes (pg. 3, para. 2). Wong teaches imidacloprid consumed was approximately 0.32-3.07 ng/bee/day (pg. 5, para. 1.). According to the instant specification 20 uL of 5 nM Imidacloprid causes learning and memory induced impairment (pg. 60, lines 25-27, pg. 62, lines 10-31). Williamson discloses sublethal amounts of imidacloprid ranging from 10 nmol/L to 100 nmol/L (1.3 ng-10.3 ng) can cause cognitive dysfunction (pg. 1800, col. 2, last para., pg. 1801, col. 2, last para). Wong teaches in sublethal diets 15 ppb (15 ug/L) imidacloprid concentrations, honeybees were administered p-coumaric acid and quercetin that reduces hazard risk (pg. 7, para. 3, pg. 8, fig. 1, pg. 6, table 2). National Pesticide Information Center discloses the molecular weight of imidacloprid is 255.7 g/mol (pg. 2, para. 2) and oral LD50 values for bees range from 3.7 ng to 40.9 ng per bee (pg. 13, para. 2). Given the molecular weight of imidacloprid 255.7g/mol and the following calculation (1x10-7mol/L(255.7g/mol))=2.557x10-5g/L=25.57ug/L), Williamson discloses sublethal amounts ranging from 2.557ug/L-25.57ug/L can cause cognitive dysfunction in honeybees. Thus Wong teaches administration of sublethal imidacloprid that is in sufficient dose to cause cognitive dysfunction in bees. Although Wong does not specifically disclose protection against impairment of cognitive function, the discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer (See MPEP 2112 (I)). Given that the doses of imidacloprid administered are sublethal yet enough to cause cognitive dysfunction and the doses of p-coumaric acid and/or quercetin are comparable to the doses claimed, the protection from cognitive dysfunction necessarily results from the method of Wong, absent evidence to the contrary.
Wong does not teach wherein the composition is administered prophylactically, i.e. before the insect pollinators are exposed to the pesticide as instantly claimed. As discussed above, Wong teaches co-administration of the p-coumaric acid or quercetin along with the pesticide imidacloprid. Wang does not teach wherein the composition is administered to insect pollinators between 1 hour and 10 days or 1 and 3 days before exposure to the pesticides.
However, Wong teaches consumption of imidacloprid and sugar water during the entire experimental period might negate the phytochemical “rescue effect” and that the protective effects of phytochemicals against imidacloprid build up over a longer period of time to provide beneficial effects against imidacloprid (pgs. 9-10, bridging para.). Wong teaches that protective effects of phytochemicals against imidacloprid build up over a longer period of time than within the 24-48 hour timeframe used in the acute toxicity bioassays (pg.9, last para.). Wong teaches that imidacloprid manifests itself through a delayed reaction compared to other pesticides and its metabolites persist longer and are more toxic than imidacloprid (pg. 10, para. 1). Wong teaches that competition between phytochemicals and pesticides for access to the enzyme catalytic sites may reduce the beneficial effects of phytochemicals (pg. 9, para. 3). Wherein administration time has an impact on the protective effects of phytochemicals to detoxify pesticides, and the prior art suggests greater than 48 hours is required for effective protection, time of administration is a result effecting variable. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. (SEE MPEP 2144.05 (II).
Taken together it would have been prima facie obvious to a person of ordinary skill in the art to modify the method of Wong such that the quercetin/p-coumaric acid formulation is administered prophylactically greater than 48 hours, before the insect pollinators are exposed to the pesticide formulation as suggested by Wong. A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success in in order to build up protective effects against imidacloprid as suggested by Wong. This method would necessarily result in the claimed protective benefits considering the composition comprises the claimed ingredients in the claimed concentrations. Wherein the prior art teaches greater than 48 hours, a person of ordinary skill in the art could arrive at the claimed administration ranges as recited by instant claims 62-63 through routine optimization.
Claims 8-9, 12-14, 18-20, and 33-34 are rejected under 35 U.S.C. 103 as being unpatentable over Wong (PLoS One, 2018, IDS filed August 10, 2023), Williamson (J. Experimental Biology, 2013, IDS filed August 10, 2023), and National Pesticide Information Center (Imidacloprid, 2018, cited in previous action) as applied to claims 1, 5-6, 37, and 61 above in view of Johnson (PLoS One, 2012, IDS filed August 10, 2023) as evidenced by Charreton (PLoS ONE, 2015, IDS filed August 10, 2023).
Regarding claims 8-9, 12-14, 18-20, and 33-34: As discussed above, Wong renders obvious the method of claims 1 and 5-6.
Wong does not teach wherein the area occupied by insect pollinators is also occupied with insect pests and exposing the pollinators to the pesticide by treating the area occupied by both pollinator and insect pest with the pesticide. Wong does not teach wherein the insect pollinators are administered the composition in the same area or separate area from the pesticide. Wong does not teach wherein the area is treated with a pesticide that is effective to reduce the number of pests, is lethal to insect pests and sublethal to insect pollinators.
However, Johnson teaches a method of protecting honey bees (i.e. insect pollinator) from imidacloprid or tau-fluvalinate (i.e. pesticide) comprising administering a bee candy composition (i.e. food for ingestion) comprising quercetin (abstract, pg. 3, table 1, pg. 6, col. 1, paras. 4-5, col. 2, paras. 3-4). Johnson teaches that quercetin is a flavonol that occurs widely in plant nectars, pollen and honey (pg. 3, col. 1, para. 2). The bees were fed the bee candy and treated topically with the pesticide at sub-lethal doses (i.e. between the LD25 and the LD50, pg. 6, col. 2, paras. 3-4). Johnson teaches the bees were treated topically with 3, 5, and 10 µg tau-fluvalinate or 0.005, 0.01, or 0.03 µg imidacloprid (pg. 6, col. 2, para. 4). Johnson teaches sublethal effects of pesticide exposure (e.g., neonicotinoids) are suspected of causing reductions in hive viability (pg. 1, col. 2, para. 1). According to Charreton, sublethal doses of tau-fluvalinate at 33 ng cause a loco-motor deficit in honeybees (pg. 1, abstract). Thus, the dose of Johnson is enough to cause cognitive (motor) impairment. Johnson teaches tau-fluvalinate is safely used in-hive by beekeepers to control Varroa mites (i.e. lethal to insect pests, sub lethal to pollinator, pg. 2, col. 1, para. 2). Johnson teaches quercetin significantly decreased the toxicity of tau-fluvalinate to bees (i.e. a protective effect, pg. 3, col. 1, para. 3, table 1). Based on the teachings of Wong and Johnson, a person of ordinary skill would recognize the benefit of treating honey bees with quercetin that may come into contact with pesticides applied to hives maintained by beekeepers.
Taken together, it would have been prima facie obvious to modify the method of Wong, such that an area occupied by the insect pollinator have been or will be treated with a pesticide, such as tau-flauvinate or imidacloprid to control insect pests is used in the method, such as a beehive maintained by beekeepers as taught by Johnson. A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success in order to protect honeybees (sublethal) from the pesticide while controlling insect pests (lethal), such as Varroa mites. As best understood by the 112(b) rejections above, wherein an entire hive is treated with pesticides, both same area and different area of pesticide application is encompassed.
Claims 59-60 are rejected under 35 U.S.C. 103 as being unpatentable over Wong (PLoS One, 2018, IDS filed August 10, 2023), Williamson (J. Experimental Biology, 2013, IDS filed August 10, 2023) and National Pesticide Information Center (Imidacloprid, 2018, cited in previous action) as applied to claims 1, 5-6, 37, and 61 above in view of Krizkova (Interdisc Toxicol, 2009, cited in previous action).
Regarding claims 59-60: As discussed above, Wong renders obvious the method of claim 1. Wong teaches certain phytochemicals, including quercetin and p-coumaric acid, are ubiquitous in the honey bee diet and are known to upregulate cytochrome P450 genes encoding enzymes that detoxify insecticides. (pg. 1, background).
Wong does not teach wherein the phenolic compound is rutin.
However, Krizkova teaches that rutin is a glycosylated version of the aglycone quercetin and both can increase CYP activities (pg. 202, col. 2, last. Para. pg. 202, figure 1., pg. 203, figs. 2-3, col. 1, para. 1).). Both quercetin and rutin are considered flavonoids (pg. 202, fig. 1). Flavonoids as a general class are recognized in the art to modulate the activity of cytochromes P450 (pg. 204, col. 1, para. 1).
Taken together it would have been prima facie obvious to modify the method of Wong such that quercetin is replaced with rutin as taught by Krizkova. A person of ordinary skill in the art would have the motivation to do so as rutin is a glycosylated version of quercetin that is known to interact/modulate P450 pathways. A person of ordinary skill in the art would have had a reasonable expectation of success as the art recognizes upregulation of cytochrome P450 is beneficial to detoxify insecticides and rutin possesses this characteristic. Wherein rutin and quercetin are flavonoids capable of modulating cytochrome activities, it is prima facie obvious to substitute equivalents known for the same purpose (see MPEP 2144.06 (II)).
Response to Arguments
Applicant’s arguments filed February 23, 2026 have been fully considered but they are not persuasive.
On pages 7-8 of Applicant’s response, Applicant argues that Wong investigates toxic effects of imidacloprid in the presence of phytochemical compounds, including p-coumaric acid and/or quercetin, however to conduct these studies Wong exposes honeybees to imidacloprid and the phytochemicals simultaneously, whereas the newly amended claims recite a prophylactic method in which the composition is administered prior to pesticide exposure (pgs. 7-8, bridging para., pg. 8, para. 2).
However, selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results (See MPEP 2144.04 (IV)). While Wong is an experimental study, Wong specifically teaches that the amount of imidacloprid was chosen to mimic concentrations encountered by bees under field conditions (pg. 5, para. 1). A person of ordinary skill in the art would recognize the eventual application of the method to be a prophylactic one, as in field conditions honey bees are not meant to be directly administered pesticides. Wong supports this by stating pesticides such as imidacloprid have been a focus of attention in colony decline of the honey bee, wherein honey bees are exposed to the pesticide via the consumption of nectar and pollen (i.e. field conditions, pg. 2, introduction, para. 1). Furthermore, Wong suggests consumption of imidacloprid and sugar water during the entire experimental period might negate the phytochemical “rescue effect” and that the protective effects of phytochemicals against imidacloprid build up over a longer period of time to provide beneficial effects against imidacloprid (pgs. 9-10, bridging para.).
On page 8 of Applicant’s response, Applicant points to the Declaration of Rivera, filed February 23, 2026, which argues Wongs protocol relies on co-administration of pesticide and phytochemicals and evaluates only survival and longevity endpoints (para. 3). Applicant argues the claimed method differs in that requires administration of the composition before pesticide exposure and is not a mere adjustment of dose or treatment conditions and instead defines a different method of use in which pollinators are biologically prepared prior to pesticide challenge (para. 4). In the declaration of Rivera (bullet point 10), the declaration argues that survival and cognitive function in bees are distinct endpoints and are not interchangeable, and cognitive function can be impaired even when no immediate mortality is observed. The declaration argues sublethal exposure to pesticides can produce cognitive and behavioral deficits without causing immediate death. The declaration argues cognition is directly tied to colony-level survival because honeybees fitness depends on complex learned and coordinated behaviors rather than mere individual viability. Cognitive impairment of honeybees leads to the infamous Colony Collapse Disorder. The declaration concludes bullet point 10 by arguing preservation of cognition is biologically distinct from preventing acute mortality, and a method that only improves short-term survival without protecting neural and cognitive function may prevent immediate death but still renders the bees functionally impaired which can ultimately result in colony collapse. In short bullet point 10 of the declaration is arguing that the instantly claimed method is directed towards preventing/reducing cognitive function whereas the prior art relied upon is intended to improve overall survival and longevity. Wong did not explicitly teach the method was for the purpose of combating cognitive impairment that results from exposure to pesticides. On page 6 of the declaration (bullet point 11), the declaration argues that Wong evaluates toxic effects in the presence of phytochemical compounds in which honeybees are exposed to imidacloprid and the phytochemicals at the same time and measures endpoints using survival and longevity metrics, including mortality rates, LC50 values, and hazard ratios.
However, while Wong presents data related to survival/longevity, Wong teaches in sublethal diets 15 ppb (15 ug/L) imidacloprid concentrations, honeybees were administered p-coumaric acid and quercetin that reduces hazard risk (pg. 7, para. 3, pg. 8, fig. 1, pg. 6, table 2). Although Wong does not teach the ability of the composition to reduce cognitive impairment, mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention. (See MPEP 2145 (II)). Thus wherein it would have been obvious to administer the composition of Wong which anticipates the claimed composition, to honey bees prior to exposure to imidacloprid, a pesticide known in the art to cause cognitive impairment, the resulting decrease in cognitive impairment (or improvement thereof) necessarily results as a result of practicing the method.
On page 6 of the declaration of Rivera (bullet point 12), the declaration argues that Wong reports that the interaction between phytochemicals and pesticide toxicity is concentration-dependent and biphasic. Wong also distinguishes between acute and chronic exposure and reports that the phytochemicals do not change acute toxicity LC50 values but improves longevity in some chronic toxicity assays. The declaration cites Wong, which states, “In chronic toxicity longevity bioassays, phytochemicals enhanced honey bee survival at low imidacloprid concentrations (15 and 45 ppb) but had a negative effect at higher concentrations (105 ppb and 135 ppb).”.
However, as discussed above, this amount of imidacloprid is a sublethal amount that is in sufficient dose to cause cognitive dysfunction in bees. Thus a person of ordinary skill in the art would recognize the benefit of administering these phytochemicals to honeybees that could be exposed to low amounts of imidacloprid for the benefit of improving survival, that necessarily reduces cognitive impairment caused by such exposure.
On pages 6-7 of the declaration (bullet point 13), the declaration argues that the claimed method requires prophylactic administration of the composition before pesticide exposure. This approach biologically primes bees with the composition which induces protective neural and physiological responses in advance, including receptor-level effects that support neural resilience. The declaration points to Example 8 which demonstrates that quercetin and rutin bind to the same receptor site as imidacloprid and stabilize receptor conformation, and the treatment with flavonoids before exposure reduces the probability and duration of pesticide-induced receptor overstimulation. The declaration argues that Wong’s experiments rely solely on co-administration of pesticide and phytochemical, and these conditions do not advantageously occupy the receptors ahead of pesticide arrival, thus, although the bees survive, their cognitive function was most likely still impaired. On page 7 of the declaration (bullet point 14), the declaration argues that prior phytochemical exposure increases receptor occupancy by phytochemicals which reduces the likelihood and persistence of subsequent imidacloprid binding and overstimulation, thereby reducing downstream neural overstimulation and cognitive impairment. The declaration argues that pretreatment establishes a protective neural state in which receptor activation patterns and signaling pathways are moderated before pesticide exposure occurs, in which additional protective responses, including the neuroprotective effects are enhanced. In short, the declaration argues pretreatment negates the negative effect of imidacloprid and enhances protective effects.
However, as discussed above, Wong suggests this, Wong suggests consumption of imidacloprid and sugar water during the entire experimental period might negate the phytochemical “rescue effect” and that the protective effects of phytochemicals against imidacloprid build up over a longer period of time to provide beneficial effects against imidacloprid (pgs. 9-10, bridging para.). Thus, a person of ordinary skill in the art would have had the motivation to administer the composition prior to exposure in order to build up protective effects against imidacloprid.
On pages 10-11 of Applicant’s response, Applicant repeats the arguments discussed above wherein Wong’s experimental design is expressly based on co-administration whereas the present claims require prophylactic administration. Applicant argues the declaration demonstrates that pretreatment with flavonoids binds to a receptor which reduces pesticide binding and overstimulation. On page 12 of Applicant’s response, applicant states that this effect is not present during co-administration of phytochemicals and pesticide.
See response to arguments above, wherein Wong suggests to administer the composition prior to exposure in order to build up protective effects against imidacloprid.
On page 12 of Applicant’s response (para. 3), Applicant argues that for claims to be rejected under USC 102, the prior art must disclose each and every element of the claims.
However, while the 102 rejections of claims 1 and 5-6 over Wong have been withdrawn as not teaching prior administration, the 102 rejections of composition claims 37 and 61 are maintained. The Examiner notes that it is well settled that “intended use” of a composition or product, e.g., “for prophylactic administration”, “to protect against impairment”, will not further limit claims drawn to a composition, so long as the prior art discloses the same composition comprising the same ingredients in an effective amount, as the instantly claimed (See MPEP 2111.02 (II)). Wherein the composition of Wong can be administered at a different time, it necessarily is suitable for prophylactic administration, absent evidence to the contrary.
On page 15 of Applicant’s response (para. 2), Applicant argues the teachings of Wong and Johnson would not have led one of ordinary skill in the art to expect the prophylactic cognitive protection or neuroprotection as claimed. Applicant argues that the Examiner’s rationale improperly assumes that survival-based outcomes and preservation of cognition are equivalent and predictable when they are different biologically endpoints. Applicant argues that the claimed prophylactic administration prior to pesticide exposure would produce the unexpected neural and cognitive protection demonstrated in the instant application. On pages 15-16 of Applicant’s response (bridging para.), Applicant points to the declaration of River (declaration bullet point 10), which describes cognition and survival rate are different biological endpoints. On page 16 of Applicant’s response (para. 2), Applicant argues neither Wong nor Johnson identify cognition as a target endpoint but are directed towards toxicity mitigation, which is different from mortality, longevity, or acute toxicity. Thus, they would not have been motivated to pursue cognitive endpoints or to expect that the claimed prophylactic method would achieve such neuroprotective results. On page 17 of Applicant’s response, Applicant argues unexpected results should be considered before arriving at a conclusion regarding obviousness to avoid improper hindsight analysis. Applicant is arguing that the protection against cognitive impairment claimed is an unexpected result that would not have been expected by a person of ordinary skill in the art.
However, the argument is not that a person of ordinary skill in the art would expect the cognitive protection, but rather this result necessarily flows as a result of practicing the method of Wong. Wherein the method is directed at reducing toxicity, of which cognitive decline is an effect of, the treatment of Wong necessarily results in neuroprotection when administered prophylactically. In order for unexpected results to be found persuasive, there needs to be a direct nexus for what is claimed and the unexpected result, and how it flows differently from the method of the prior art (see MPEP 716.01(b)). In the instant case, the method of combating toxicity with the claimed composition necessarily results in the cognitive improvement. Mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention. (See MPEP 2145 (II)). Additionally, Johnson teaches quercetin significantly decreased the toxicity of tau-fluvalinate to bees (i.e. a protective effect, pg. 3, col. 1, para. 3, table 1) and the art recognizes tau-flavinate results in motor deficits and detoxification of this pesticide would necessarily combat this. The Examiner also notes that unexpected results must also be commensurate with the scope of the claims (See MPEP 716.02(d). The instant specification demonstrates the therapeutic benefit of rutin or quercetin on imidacloprid exposure of honeybees (pg. 58, lines 5-16). The instant claims include prophylactically treating insect pollinators with one or more flavonols, a large class of possible compounds, and pesticides generally. Thus, even if the unexpected results were to be found persuasive, they would not be commensurate with the scope of the claims.
On page 18 of Applicant’s response, Applicant argues Wong teaches coadministration and does not teach prophylactic treatment. Applicant argues Johnson does not teach prophylactic administration and did not measure cognitive endpoints. On page 19 of Applicant’s response, Applicant repeats the arguments discussed above in the declaration which teach prophylactic administration results in protective effects via reduction of pesticide receptor binding. On page 20 of Applicant’s response, Applicant argues co-exposure does not allow for neural priming necessary for preservation of cognitive function (para. 1). Applicant argues Wong’s results are concentration dependent outcomes, wherein different concentration can worsen outcomes instead of providing benefit. On pages 20-21 of Applicant’s response, Applicant argues the preservation of cognition achieved through prophylactic administration reflects a mechanistically distinct outcome that neither reference recognizes, measures, nor predicts.
However, as discussed previously, Wong suggests consumption of imidacloprid and sugar water during the entire experimental period might negate the phytochemical “rescue effect” and that the protective effects of phytochemicals against imidacloprid build up over a longer period of time to provide beneficial effects against imidacloprid (pgs. 9-10, bridging para.). Thus, a person of ordinary skill in the art would have had the motivation to administer the composition prior to exposure (i.e. prophylactically) in order to build up protective effects against imidacloprid. Wong teaches in sublethal diets 15 ppb (15 ug/L) imidacloprid concentrations, honeybees were administered p-coumaric acid and quercetin that reduces hazard risk (pg. 7, para. 3, pg. 8, fig. 1, pg. 6, table 2). The amount of imidacloprid was chosen to mimic concentrations (i.e. sublethal) encountered by bees under field conditions (pg. 5, para. 1). Thus the benefit is acknowledged in sublethal concentrations which don’t kill the honey-bees outright.
On pages 21-22 of Applicant’s response, Applicant argues the claimed invention is not one of routine optimization but an unexpected finding establishing prophylactic treatment leads to a change in the underlying pathways that manage pesticide exposure, which found that the timing of the treatment could be adjusted to improve neuroprotection.
However, as discussed above, Wong suggests consumption of imidacloprid and sugar water during the entire experimental period might negate the phytochemical “rescue effect” and that the protective effects of phytochemicals against imidacloprid build up over a longer period of time to provide beneficial effects against imidacloprid (pgs. 9-10, bridging para.). Thus, a person of ordinary skill in the art would have had the motivation to administer the composition prior to exposure (i.e. prophylactically) in order to build up protective effects against imidacloprid. This ultimately suggests timing of administration is imported to exhibiting the protective effects of the phytochemicals.
On page 22 of Applicant’s response, Applicant concludes that Wong and Johnson cannot be interpreted to suggesting the claimed prophylactic method and there is no disclosure that administration would confer the cognitive benefits achievable by the claimed method.
However, as discussed above, Wong suggests consumption of imidacloprid and sugar water during the entire experimental period might negate the phytochemical “rescue effect” and that the protective effects of phytochemicals against imidacloprid build up over a longer period of time to provide beneficial effects against imidacloprid (pgs. 9-10, bridging para.). Thus, a person of ordinary skill in the art would have had the motivation to administer the composition prior to exposure (i.e. prophylactically) in order to build up protective effects against imidacloprid. This method would necessarily result in the claimed protective benefits considering the composition comprises the claimed ingredients in the claimed concentrations.
Applicant’s reply is considered to be a bona fide attempt at a response and is being accepted as a complete response. The 35 USC § 112, 102, and 103 rejections are maintained for reason of record and foregoing discussion.
Conclusion
No claims are allowed in this action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMUEL L GALSTER whose telephone number is (571)270-0933. The examiner can normally be reached Monday - Friday 8:00 AM - 5:00 PM.
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/SAMUEL L GALSTER/Examiner, Art Unit 1693