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 .
Priority
This application is a national stage entry of PCT/EP2020/086102 filed on 12/15/2020. Acknowledgment is made of applicant's claim for foreign priority based on an application filed in EUROPEAN PATENT OFFICE (EPO) (19216378.0) on 12/16/2019.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Response to Amendment
Applicant’s amendment filed December 9, 2025 amending claim 16, and canceling claim 18 has been entered. Claims 1-15 were previously canceled. Claims 16, 17 and 19-25 are currently pending and presented for examination.
Response to Arguments
Applicant's arguments and declaration under 37 CFR 1.132 filed December 9, 2025 have been fully considered but they are not persuasive.
Applicant argues that chewing lice are typically treated by pour on (topical) parasiticides and oral or parental administration of parasiticides have been found to be ineffective in controlling chewing lice infestations in livestock animals. Applicant further presents a declaration under 37 CFR 1.132 which states that the standard practice for treating chewing lice is with topical products. The declarant also reviewed several literature references that discuss the problems when chewing lice are treated with parasiticides that are administered orally or parentally and how treating chewing lice infestations results in the lice receiving a sublethal dose of the parasiticide resulting in ineffective control of the chewing lice. The declarant discusses Lifschitz which teaches that macrocyclic lactones (ML), a known class of parasiticides, are effective against the sucking lice when administered subcutaneously but not for chewing lice which are not fully eliminated by this mode of administration, likely because chewing lice feed on scrapings of outer skin and are therefore exposed to lower levels of the parasiticide whereas the sucking lice consume a higher level of the parasiticide while consuming their blood meal. The declarant also discusses Campbell which describe additional examples of the lack of efficacy of injectable parasiticides in controlling chewing lice infestations in cattle as compared to pour on formulations which have eliminated the problems with chewing lice. Applicant further argues that some commercially available injectable parasiticides contain label warnings about the lack of efficacy against chewing lice (e.g. Dectomax® doramectin injection package insert, lower left hand corner).
Applicant argues that understanding the industry preference for treating chewing lice with topically administered parasiticides, one skilled in the art would not be motivated by the teachings of Lahm to administer fluralaner by subcutaneous administration. Applicant argues that the skilled person knowing the preference for topical application of parasiticides to treat chewing lice and the absence of any guidance in Lahm as to any topical application let alone for chewing lice versus sucking parasites would not be motivated by Lahm's disclosure to try subcutaneously administered fluralaner to treat a chewing lice infestation.
Applicant further argues that when evaluating the subcutaneously injected fluralaner as a treatment for chewing lice infestation, the high efficacy of the claimed method of treatment was surprising as this parasite is not a blood feeder and feeds on skin scurf and debris, and thus these results were unexpected.
These arguments are found not persuasive because Lahm does not teach or suggest topical administration for the treatment of any ectoparasite disclosed therein. In fact the purpose of Lahm is to control animal parasites in animal health, especially in the areas of food production and companion animals, by avoiding existing methods of treatment and parasite control (page 2 lines 12-19). Lahm specifically teaches that the discovery of more effective ways to control animal parasites is imperative and that it is advantageous to discover ways to apply pesticides to animals orally or parenterally so as to prevent the possible contamination of humans or the surrounding environment (page 2 lines 12-19). Lahm specifically teaches a method for protecting animals from a parasitic invertebrate pest comprising orally or parenterally administering to the animal a pesticidally effective amount of a compound of Formula 1:
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(pages 2-3). Lahm teaches that a preferred compound of Formula 1 is fluralaner 4-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-2methyl-N-[2-oxo-2-[(2,2,2-trifluoroethyl)amino]ethyl]benzamide (page 13 lines 32-33 and page 4 lines 25-32). Lahm teaches that the compounds of Formula 1 may be administered in a controlled release form, for example in subcutaneous or orally administered slow release formulations (page 63 lines 18-19). Thus Lahm does not teach or suggest topical administration and only teaches administration forms that require sufficient drug levels in the blood.
Furthermore, Applicant’s arguments and declaration are found not persuasive since none of the references discussed teach that all compounds administered by subcutaneous administration were completely ineffective against biting or chewing parasites. Each of the references cited disclose some effect when administered by subcutaneous injection. It is noted that claim 16 of the instant application merely requires the subcutaneous administration of fluralaner to treat or protect a ruminant animal from chewing lice infestation and there is no requirement for total elimination of the chewing lice. Furthermore, the claim utilizes comprising language which does not exclude the co-administration of other compounds or additional steps which administer other compounds by other routes of administration.
In addition, based on the references cited, it is clear that the efficacy depends upon the drug, its formulation and how it is able to distribute to the skin layer in sufficient amounts to control the ectoparasite. None of the references provided by Applicant discuss fluralaner or other similar compounds belonging to the isoxazoline class of drugs. Thus Applicant does not provide any evidence that fluralaner or any other isooxazoline compound would have been expected to have the same results as the other pesticidal compounds discussed.
Furthermore, in order to rebut Applicant’s assertion that the skilled artisan would not have expected control of biting or chewing pests in ruminant animals by the subcutaneous injection of the pesticide based on references well before the effective filing date of the claimed invention (Campbell et al. 2001; Chick et al. 1993) and a reference which is not prior art (Lifschitz et al. 2024), Applicant’s attention is directed to Ajith et al. Published Jan. 30, 2019 (Ajith, Y., Dimri, U., Gopalakrishnan, A. & Devi, G., 2019, ‘A field study on the efficacy of ivermectin via subcutaneous route against chewing lice (Bovicola caprae) infestation in naturally infested goats’, Onderstepoort Journal of Veterinary Research 86(1), a1635), which provides a more appropriate date to establish the state of the art prior to the effective filing date of the claimed invention. Ajith et al. teaches that successful control of chewing lice in goat herds depends on the method of application and efficacy of insecticide, which, in turn, depends on the distribution of insecticide on the body surface and redistribution to untreated parts (page 1). Ajith et al. teaches that failure in treatment may occur because of incorrect application, inability to reach effective licicidal concentration on skin surface and development of insecticidal resistance (page 1). Ajith et al. teaches that conventionally, topical insecticides such as amidines, organophosphates, carbamates and pyrethroids were used as dips or spray to control chewing lice infestation in animals, but low safety (potential for being toxic to the domestic animals), public health concerns (topical preparations can spread to animal handlers), practical difficulties (the distribution of insecticide depends on hair length and external application is not suitable because Caprine pediculosis is more prevalent during winter season) and risk of environmental contamination (goats are mainly reared under extensive rearing system, especially in India, so topically applied insecticide may get spread into the pasture) limited their therapeutic use in food animals, especially those reared under an extensive grazing system (pages 1-2). Ajith et al. further teaches other negatives associated with topical administration of pesticides (page 2). Ajith et al. specifically demonstrates that ivermectin administered subcutaneously was found effective in controlling chewing lice infestation on goats (page 3). Thus, contrary to other older studies, Ajith et al. shows complete clearance of lice infestation in all animals by day 14 after subcutaneous ivermectin therapy and the treated animals remained uninfected from day 14 to day 21, even when the maximum chance for natural transmission from infested untreated animals was provided (page 5).
Thus based on the teachings of Lahm et al. which teaches treating ectoparasites including biting and chewing lice in ruminant animals comprising the administration of subcutaneous injection of fluralaner, and in view of the state of the art prior to the effective filing date of the claimed invention, which demonstrates that it is possible to treat and control chewing and biting lice in ruminant animals by subcutaneous injection of pesticides, it would have been obvious to a person of ordinary skill in the art to treat ectoparasites including biting and chewing lice in ruminant animals comprising the administration of a subcutaneous injection of fluralaner with a reasonable expectation of success.
Obviousness does not require absolute predictability, only a reasonable expectation of success, i.e., a reasonable expectation of obtaining similar properties. See, e.g., In re O ’Farrell, 853 F.2d 894, 903, 7 USPQ2d 1673, 1681 (Fed. Cir. 1988). Par Pharm., Inc. v. TWi Pharms., Inc., 773 F.3d 1186, 1198 (Fed. Cir. 2014).
Accordingly, for these reasons the previous rejection under 35 USC 103 is hereby maintained and reproduced below. This action is FINAL.
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.
Claims 16, 17 and 19-25 are rejected under 35 U.S.C. 103 as being unpatentable over Lahm NZ-618248-A.
Claims 16, 17 and 19-25 of the instant application claim a method for treating or protecting a ruminant animal from Bovicola spp. chewing lice infestation comprising a single subcutaneous administration of a composition comprising an effective amount of at least one isoxazoline compound of Formula (1) such as fluralaner having the following structure:
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Lahm teaches a method for protecting an animal from a parasitic pest and parasitic pest infestation (page 2 lines 9-11).
Lahm teaches, in addition the compounds of Formula 1 may also be formulated as a depot preparation, wherein such long acting formulations may be administered by implantation (for example, subcutaneously or intramuscularly) or by intramuscular or subcutaneous injection (page 64 lines 7-10)
Lahm teaches for oral or parenteral administration to animals, a dose of a compound of the present invention administered at suitable intervals typically ranges from about 0.01 mg/kg to about 100 mg/kg, and preferably from about 0.01 mg/kg to about 30 mg/kg of animal body weight (page 66 lines 15-17). Suitable intervals for the administration of compounds of Formula I to animals range from about daily to about yearly, specifically intervals ranging from about weekly to about once every 6 months, and preferably monthly administration intervals (i.e. administering the compound to the animal once every month) (page 66 lines 18-21).
Lahm specifically teaches subcutaneous dosing with a test compound of formula (I) (page 68 lines 25-28).
Lahm does not specifically exemplify treating or protecting a ruminant animal such as cattle from Bovicola spp. chewing lice by subcutaneous administration of a compound of formula (I) such as fluralaner. Lahm does not teach chewing lice that are resistant to the compounds as claimed in claim 23.
Although Lahm does not specifically exemplify treating or protecting a ruminant animal such as cattle from Bovicola spp. chewing lice by subcutaneous administration of a compound of formula (I) such as fluralaner, Lahm specifically teaches as detailed above that the compounds of Formula 1 which include the same compounds as claimed of formula (I) including fluralaner are effective against a number of animal ectoparasites including insect and acarine pests e.g., biting insects such as flies and mosquitoes, mites, ticks, lice, fleas, true bugs, parasitic maggots, and the like, wherein lice include, sucking lice, e.g., Bovicola spp., such as Bovicola (Damalinia) bovis, and Bovicola equi (page 58 lines 30-33 and page 59 lines 13-14 and page 59 line 34-page 60 line 4). Lahm teaches compounds and compositions of Formula 1 are suitable for combating parasitic invertebrate pests that infest animal subjects including those in the wild, livestock and agricultural working animals, wherein livestock include cattle (page 56 lines 19-28). Moreover, Lahm specifically teaches that the compounds of Formula 1 may be administered in a controlled release form, for example in subcutaneous or orally administered slow release formulations (page 63 lines 18-19).
The prior art does not appear to provide sufficient specificity, i.e., involves too much "picking and choosing" to give rise to anticipation. See Coming Glass Works v. Sumitomo Elec., 868 F.2d 1251, 1262 (Fed. Circ. 1989). That being said, it must be remembered that "[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect ....the combination is obvious". KSR v. Teleflex, 127 S.Ct. 1727, 1740 (2007)(quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)). Consistent with this reasoning, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to have selected the various combinations of features claimed from within the prior art disclosure specifically, treating or protecting a ruminant animal such as cattle from Bovicola spp. chewing lice by subcutaneous administration of a compound of formula (I) such as fluralaner, to arrive at the instantly claimed subject matter. Based on the teachings of Lahm, a person of ordinary skill in the art would have been motivated to administer a compound of formula (I) such as fluralaner for the treatment or protection against Bovicola spp. chewing lice with a reasonable expectation of success.
With respect to claims 21 and 22 of the instant application, Lahm specifically teaches that suitable intervals for the administration of compounds of Formula I to animals range from about daily to about yearly, specifically intervals ranging from about weekly to about once every 6 months, and preferably monthly administration intervals (i.e. administering the compound to the animal once every month) and thus a compound being effective for 15 days or 56 days as claimed is rendered obvious in view of the cited prior art teachings (page 66 lines 18-21). Moreover, with respect to the dosages as claimed in claim 19 of the instant application, Lahm teaches preferable dosages from about 0.01 mg/kg to about 30 mg/kg of animal body weight (page 66 lines 15-17).
In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) (The prior art taught carbon monoxide concentrations of "about 1-5%" while the claim was limited to "more than 5%." The court held that "about 1-5%" allowed for concentrations slightly above 5% thus the ranges overlapped.); In re Geisler, 116 F.3d 1465, 1469-71, 43 USPQ2d 1362, 1365-66 (Fed. Cir. 1997) (Claim reciting thickness of a protective layer as falling within a range of "50 to 100 Angstroms" considered prima facie obvious in view of prior art reference teaching that "for suitable protection, the thickness of the protective layer should be not less than about 10 nm [i.e., 100 Angstroms]." The court stated that "by stating that ‘suitable protection’ is provided if the protective layer is ‘about’ 100 Angstroms thick, [the prior art reference] directly teaches the use of a thickness within [applicant’s] claimed range.").
Although Lahm does not specifically teach treating chewing lice that are resistant to any one of organophosphates, synthetic pyrethroids, neonicotinoids, spinosyn or benzoyl phenyl urea compounds, Lahm specifically teaches that the compounds of formula (I) may be administered in combination with organophosphate pesticides, and other compounds as claimed in claim 23 of the instant application (page 60 lines 8-32). Thus it would have been obvious to a person of ordinary skill in the art that the combination would be useful in the prevention of resistance or overcoming resistance of the pest to treatment. Thus in the absence of secondary considerations such as unexpected results, treating all lice including lice resistant to other compounds is rendered obvious in view of the teachings of Lahm which teaches that the compounds and combinations thereof are suitable for treating chewing lice.
Thus the cited claims of the instant application are rendered obvious in view of the teachings of Lahm.
Reference considered pertinent to the instant invention:
Ajith, Y., Dimri, U., Gopalakrishnan, A. & Devi, G., 2019, ‘A field study on the efficacy of ivermectin via subcutaneous route against chewing lice (Bovicola caprae) infestation in naturally infested goats’, Onderstepoort Journal of Veterinary Research 86(1), a1635.
Conclusion
Claims 1-15 and 18 are canceled. Claims 16, 17 and 19-25 are rejected. No claims are 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 KARA R. MCMILLIAN whose telephone number is (571)270-5236. The examiner can normally be reached Tuesday-Friday 12:00 PM-6:00 PM.
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/KARA R. MCMILLIAN/Primary Examiner, Art Unit 1623
KRM
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