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 .
Status of Action/Claims
Receipt of Remarks/Amendments filed on 3/11/2026 is acknowledged. Claims 1-2, 4, 6-22 and 24-27 are currently pending. Claims 15-20, 22, 24 and 26-27 have been withdrawn. Accordingly, claims 1-2, 4, 6-14, 21 and 25 are presented for examination on the merits for patentability.
Rejection(s) not reiterated from the previous Office Action are hereby withdrawn. The following rejections are either reiterated or newly applied. They constitute the complete set of rejections presently being applied to the instant application.
Modified Claim Rejection(s) Necessitated by Amendments
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 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Claims 1-2, 4, 6, 8-9, 21 and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Lehay et al. (WO 2015/091898 A1; Jun. 25, 2015) in view of Faassen et al. (US 8,658,687; Feb. 25, 2014).
Lehay throughout the reference teaches a composition comprising isoxazoline compound and the use of the composition to treat or prevent parasite infestation of animals (Abstract). Particularly, Lehay teaches a pharmaceutical composition comprising an isoxazoline compound of formula I and a pharmaceutically acceptable carrier (Claim 1). It teaches the isoxazoline compound is fluralaner in the amount of between 1.5mg/ml and 100 mg/ml (Claims 2 and 3). The amount of fluralener taught by Lehay equates to 0.15% to 10% w/v, which overlaps the amounts recited in instant claims 6 and 8. The reference discloses that the composition according to the invention can be in the form of an aqueous suspension (Page 19, lines 27-29). Lehay also teaches that the composition can be a parenteral composition which is administered parenterally, such as via intramuscular injection (Page 19, lines 6-11). Further, the reference teaches that the composition can be diluted with water (Page 19, lines 18-21), which reads on the claimed recitation wherein the composition is to be reconstituted with a vehicle.
The teachings of Lehay have been set forth above.
Lehay does not expressly teach the particle size distribution of isoxazoline as recited in the instant claims. Also, while Lehay teaches the composition in a suspension, Lehay does not expressly disclose the suspension comprising a suspending agent such as sodium carboxymethyl cellulose and the amount thereof. However, these deficiencies are cured by Faassen.
Faassen teaches injectable formulations comprising asenapine hemipamoate suspended particles (Title, Abstract). Faassen discloses that in injectable formulations medicament comprising a particle suspension, particle size distribution of suspended active affects the release of drug. It teaches it is known in the art that an active drug in suspensions made with particles having a smaller mean particle size provide higher Cmax in a shorter time than those suspension prepared from particle fractions having a larger mean particle size. (see: col. 2, lines 70 to col. 3, lines 1-7). The reference discloses particle fractions yielding, small d50 values (e.g. 0.25 microns) or which have a large "fines" content (10 vol % or greater of particles with less than 1 micron particle size (e.g., 1.5 micron) tend to exhibit a "bursting effect" (also termed a "Burst Release"). (see: col. 16, lines 51-57). The reference in table II discloses the d10, d50 and d90 particle size distribution in microns. It states it is preferred to remove both particles smaller than 0.3 microns and particles larger than 200 microns (col. 4, lines 42-46). Additionally, Faassen teaches using caboxymethyl cellulose as dispersing agent in the suspension formulations (col. 12, line 66 to col. 13, line 2).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have modified Lehay to incorporate the teachings of Faassen to manipulate the particle size distribution to determine the optimal particle size based on the release of active desired. One would have been motivated to do so because based on the teachings of Faassen, it was known in the art that particle size distribution affects the release of the drug and that smaller particle size leads to burst release whereas larger particle size needs to be chosen if a long lasting effect is desired. Thus, it would have been obvious to one skilled in the art to manipulate the particle size distribution of the isoxazoline compound taught by Lehay to determine the optimal particle size for the desired release. One skilled in the art would have had a reasonable expectation of success because both Lehay and Faassen disclose injectable suspension formulations. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here 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." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have modified Lehay to incorporate the teachings of Faassen to include a dispersing agent (e.g., carboxymethyl cellulose) in the suspension of Lehay. As discussed supra, Lehay teaches the composition can be a suspension and Faassen also teaches suspension compositions comprise dispersing agents such as carboxymethyl cellulose. Thus, it would have been obvious to one skilled in the art to include the known dispersing agent in a suspension because dispersing agent or suspending agents are commonly used in the suspension formulations. Further, it would have been obvious to one skilled in the art to manipulate the amount of the carboxymethyl cellulose and determine an amount that would provide an optimal dispersion of the suspension because carboxymethyl cellulose is taught by the prior art to be used as a dispersing agent. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here 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." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
With respect to the instantly claimed limitation wherein the isoxazoline compound is in suspension in the composition and particularly an aqueous suspension, as discussed supra, Lehay teaches that the composition according to the invention can be in the form of an aqueous suspension (Page 19, lines 27-29). While Lehay does not exemplify an aqueous suspension, Lehay clearly teaches an aqueous suspension being within the scope of the invention and therefore, all of the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention. Note: MPEP 2141 KSR International CO. v. Teleflex Inc. 82 USPQ 2d 1385 (Supreme Court 2007). Thus, it would have been obvious to one skilled in the art to form a suspension of the isoxazoline compound because Lehay teaches that an aqueous suspension is a suitable form of the invention and within the scope of the invention taught by Lehay.
From the combined teaching of the cited reference, one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Claims 1-2, 4, 6, 7, 8-9, 10-13, 21 and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Lehay et al. (WO 2015/091898 A1; Jun. 25, 2015) in view of Faassen et al. (US 8,658,687; Feb. 25, 2014) as applied to claims 1-2, 4, 6, 8-9, 21 and 25 above and further in view of Cady et al. (US 2016/0256442A1; Sep. 8, 2016) (Cited in IDS filed 8/13/2020).
The teachings of Lehay and Faassen have been set forth above.
Lehay and Faassen do not expressly teach wherein the isoxazoline compound is present in an amount between about 25% to about 35%. Lehay and Faassen also do not expressly teach the composition further comprises another parasiticide compound which is moxidectin. However, these deficiencies are cured by Cady.
Cady throughout the reference teaches long acting injectable formulations for combating parasites in animals, comprising at least one isoxazoline active agent (Abstract). Particularly, Cady discloses fluralaner as the isoxazoline compound (claim 10). It also teaches the composition comprising about 15% to about 40% of an isoxazoline compound (Para 0240) which overlaps the amount recited in instant claim 7. Cady teaches the composition further comprises moxidectin as an additional active ingredient (claim 24-26).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have modified Lehay to incorporate the teachings of Cady and include an amount of fluralaner taught by Cady in the composition of Lehay. One would have been motivated to do so because both Lehay and Cady teach formulations for combating parasites in animals, comprising isoxazoline active agent and Cady teaches that the instantly claimed amount of about 25% to about 35% of fluralaner was known for combating parasites in animals. Further, it would have been obvious to one skilled in the art to manipulate the amount to determine the optimal amount needed for combating parasites during routine optimization. “The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.” In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969). See MPEP 2144.05.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have modified Lehay to incorporate the teachings of Cady and further include moxidectin as an additional active ingredient as taught by Cady into the composition of Lehay. One would have been motivated to do so because both Lehay and Cady teach formulations for combating parasites in animals, comprising isoxazoline active agent and Cady teaches further adding moxidectin for combating parasites in animals. As a general principle it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose, the idea of combining them flows logically from their having been individually taught in the prior art. See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) MPEP 2144.06.
From the combined teaching of the cited reference, one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Claims 1-2, 4, 6, 7, 8-9, 10-13, 14, 21 and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Lehay et al. (WO 2015/091898 A1; Jun. 25, 2015) in view of Faassen et al. (US 8,658,687; Feb. 25, 2014) and Cady et al. (US 2016/0256442A1; Sep. 8, 2016) (Cited in IDS filed 8/13/2020) as applied to claims 1-2, 4, 6, 7, 8-9, 10-13, 21 and 25 above and further in view of Wang et al. (WO 2008/030385 A2; Mar. 13, 2008).
The teachings of Lehay, Faassen and Cady have been set forth above.
The above cited references do not teach wherein moxidectin is present in an amount between about 0.1% to about 1% as recited in instant claim 14. However, this deficiency is cured by Wang.
Wang teaches formulations for the control of parasites in animals (Abstract). It teaches the formulation comprises moxidectin in an amount of about 0.05% to about 10% which overlaps the amount recited in the instant claims.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have modified the above cited references to incorporate the teachings of Wang and include an amount of moxidectin taught by Wang in the composition of Lehay. One would have been motivated to do so because Lehay, Cady and Wang teach formulations for combating and controlling parasites in animals and Wang teaches that the instantly claimed amount of moxidectin was known to be used in formulations for combating parasites in animals. Further, it would have been obvious to one skilled in the art to manipulate the amount to determine the optimal amount needed for combating parasites during routine optimization. “The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.” In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969). See MPEP 2144.05.
From the combined teaching of the cited reference, one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Response to Arguments
Applicant's arguments filed 3/11/2026 with respect to the 103 rejections have been fully considered but they are not persuasive.
Applicant argued the claimed particle size distribution of between 75 and 130 micron and the suspending agent (sodium carboxymethyl cellulose) in the amount of 2% to 2.5% provide unexpected results. Applicant pointed to Example 2, Table 4 and Example 7 of instant specification to argue that all of these samples demonstrated unexpected result of no significant injection site reaction or irritation. Applicant stated that while some formulations with smaller particle sized fluralaner sometimes but not always exhibit significant injection site reactions, formulations with large particle sized fluralaner exhibit minor or no such adverse reactions. (see pages 14-16 of applicant remarks).
In response, as addressed in the previous office actions, firstly the data in Example 2 - Table 4 of the specification is unclear to the examiner because applicant do not clearly explain the results obtained in each sample. For example, in sample 1B, Day 3-5 states "resolved", Day 12-14 states "none" and Day 7-9 does not state anything. It is unclear what these results in the table represent and the specification fail to clearly explain. Similarly, it appears that sample 1E results show there being irritation on days 0-2 and 3-5 but the boxes from days 7-19 are empty and then box with day 20-21 appears to show there being irritation. The specification do not clearly explain what the empty boxes represent and what the results that show up after empty boxes mean. Also, while on last paragraph of page 39, applicant state the data present the number of dogs with injection site irritation, size and duration, it is unclear to the examiner what each number or the result for each sample on the particular days represent.
Additionally, instant claim 1 recites the particle size of 75 micron to 130 micron. The data in Table 4 shows results for 5-40 micron and 100 micron. There is no data provided on the injection site irritation when the particle size is for example 75 micron (which is the lower limit of the claimed range), 130 micron (which is the upper limit of the claimed range), or 140 micron (which above the claimed upper limit) and thus there is no evidence that when the particle size increases from 40 micron to 75 micron, the injection site irritation is unexpectedly reduced, or that there would be injection site irritation when the particle size is 140 micron but not at 130 micron. As stated in MPEP 716.02 (d): To establish unexpected results over a claimed range, applicants should compare a sufficient number of tests both inside and outside the claimed range to show the criticality of the claimed range. In re Hill, 284 F.2d 955, 128 USPQ 197 (CCPA 1960). The data in the specification provide only one sample inside the claimed range, which is 100 micron particle size, and this is insufficient to show unexpectedness of the claimed range which is 75 to 130 microns. Also, the unexpected results have to be of statistical and practical significant and the current data provided by the applicant fails to clearly show that the results are of statistical and practical significance.
Further, the comparative data in specification does not appear to be a single variable comparison because none of the examples in Table 3 show that the only difference between example 1J (inventive example) and the comparative examples is the difference in particle size and concentration of NaCMC. Specifically, there are different components used in example 1J and comparative examples and there does not appear to be a single variable comparison. For example, Examples 1E to 1H comprise Lecithin and NaCitrate and example 1J does not comprise these components. Therefore, it is unclear whether these difference are what affects the injection site irritation and drug’s release rate.
Moreover, the results of some of the comparative examples (e.g. example 1I and 1B) appear to be the same as example 1J because there appears to be no data after day 0-2, which is similar to example 1J. Therefore, applicant arguments and data regarding unexpected results does not appear to persuasive at this time.
Applicant in the remarks referred to the previous declaration of Mr. Matthew Notta (October 24, 2023) to argue that the data of example 2, table 4 and example 7 demonstrate the lack of significant injection site irritation or reaction.
In response, with respect to the declaration by Notta (October 24, 2023), while the declaration provides more data which shows that the examples where particle size distribution ranges from 75 micron to 130 micron results in significantly less injection site reaction, the examiner again argues that the data provided is not a single variable comparison and thus it is unclear whether it is the particle size distribution or other variable that affect the injection site reaction when the composition is administered. For example, applicant refer to example 5 of the specification wherein example 5 includes particles sizes ranging from 77 micron to 130 micron. In example 5, the amount of fluralaner used is 15%. For comparative data, applicant refer to the results in example 1. In example 1, the comparative compositions comprise fluralaner in an amount of 7.5% which is half of the amount used in example 5. Since the amount of the fluralaner used is different in the experimental and comparative examples, it is unclear whether the injection site reaction is due to the particle size distribution or whether it is due to the different concentration of fluralaner used in the composition. As discussed in the office action dated 12/20/2023, Leung et al. (Hindawi Publishing Corporation, Vol. 2015, Dec. 2015) discloses that risk of injection site reactions can be influenced by multiple factors which include dose and drug concentration (see: Introduction). Since the amount of the drug was known to influence the injection site reaction in a subject, and the data provided by the applicant varies the amount of the active agent, it cannot be determined whether the effect on the injection site reaction is due to the different amount of the active drug or whether it is due to the particle size distribution. The applicant should bring forth data which is a single variable comparison and which clearly shows that the unexpected result is due to the particle size distribution claimed in the instant claims.
Additionally, independent claim 1 does not recite any particular concentration of fluralaner and dependent claim 6 recites a concentration ranging from 5% to 50%. The data provided by applicant shows concentration of fluralaner being 15%, however, it is unclear whether amounts of fluralaner which are outside of the 15% amount would still result in similar results in terms of injection site reaction. Thus, applicant’s data which utilizes only 15% of fluralaner does not appear to be commensurate in scope with the instant claims because the instant claims recite amounts of fluralaner which are much broader in scope than the amount in the examples provided.
Applicant in the remarks also referred to the previous second declaration of Mr. Matthew Notta (February 6, 2025) which argued that solution formulations of fluralaner are not suitable for parenteral administration due to moderate to severe injection site reactions. In the declaration by Mr. Notta, it was argued that none of the solution formulations were found to be acceptable due to injection site intolerance.
In response, firstly the experimental data in the declaration provides results for intradermal and subcutaneous injection administration. As discussed supra, Lehay teaches the composition may be administered parenterally via intramuscular injection, intravenous injection, subcutaneous injection. While Lehay teaches subcutaneous injection administration, Lehay does not teach intradermal injection administration. Therefore, the examiners response will focus on the results for subcutaneous administration since Lehay does not teach intradermal administration. With regards to the argument that solution formulations were found to be unacceptable due to injection site intolerance, the examiner argues that majority of the results for subcutaneous administration showed there being zero injection site intolerance. For test article 1, 4 out of the 6 dogs had 0 injection site intolerance. For test article 2, 3 out of the 6 dogs had 0 injection site intolerance. For test article 3, 4 out of the 6 dogs had 0 injection site intolerance. For test article 4, 6 out of the 6 dogs had 0 injection site intolerance. For test article 5, 5 out of the 6 dogs had 0 injection site intolerance. For test article 6, 2 out of the 6 dogs had 0 injection site intolerance. For test article 7, 4 out of the 6 dogs had 0 injection site intolerance. For test article 8, 3 out of the 6 dogs had 0 injection site intolerance. The results show that majority (31 out of 48) of the subcutaneous administrations had zero injection site intolerance. Further, the 8 test articles prepared and administered do not all have the same ingredients (other than the active fluralaner ingredient) and it is unclear whether the different ingredients in the different test articles influenced the injection site reaction. Moreover, there is no comparative data which compares the suspension formulation with the solution formulation using similar ingredients and/or a single variable comparison between the suspension form and the solution form. Therefore, the results provided by the applicant do not appear to have established the superior performance of suspension form with respect to injection site reactions.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-2, 4, 6-14 , 21 and 25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4-5, 15-17 and 23-28 of copending Application No. 17/999,024 in view of Lehay et al. (WO 2015/091898 A1; Jun. 25, 2015), Cady et al. (US 2016/0256442A1; Sep. 8, 2016) (Cited in IDS filed 8/13/2020) and Faassen et al. (US 8,658,687; Feb. 25, 2014).
The ‘024 application claims an injectable pharmaceutical composition comprising microspheres which include about 1% to about 40% of macrocyclic lactones and the composition comprises isoxazoline compound and an aqueous carrier, wherein the microspheres and the particles of the compound are suspended in the aqueous carrier. The composition comprises a suspending agent which is carboxymethyl cellulose. The macrocyclic lactone is moxidectin. ‘024 also claims the particle size distribution is from about 8 micron to about 250 micron. The isoxazoline compound comprises fluralaner.
The ‘024 application does not claim the amount of the isoxazoline compound. However, this deficiency is cured by Lehay and Cady.
As discussed supra, Lehay teaches the isoxazoline compound is fluralaner in the amount of between 1.5mg/ml and 100 mg/ml (Claims 2 and 3). The amount of fluralener taught by Lehay equates to 0.15% to 10% w/v, which overlaps the amounts recited in instant claims 6 and 8.
As discussed supra, Cady discloses fluralaner as the isoxazoline compound (claim 10). It also teaches the composition comprising about 15% to about 40% of an isoxazoline compound (Para 0240) which overlaps the amount recited in instant claim 7.
The ‘024 application does not claim the thickness recited in the instant claims. However, Faassen cures this deficiency.
Faassen teaches it is known in the art that an active drug in suspensions made with particles having a smaller mean particle size provide higher Cmax in a shorter time than those suspension prepared from particle fractions having a larger mean particle size. (see: col. 2, lines 70 to col. 3, lines 1-7). The reference discloses particle fractions yielding, small d50 values (e.g. 0.25 microns) or which have a large "fines" content (10 vol % or greater of particles with less than 1 micron particle size (e.g., 1.5 micron) tend to exhibit a "bursting effect" (also termed a "Burst Release"). (see: col. 16, lines 51-57).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have modified ‘024 to incorporate the teachings of Lehay and Cady and include an amount of fluralaner taught by Lehay and Cady in the ‘024 composition. One would have been motivated to do so because ‘024 is silent on the amount of isoxazoline compound and Lehay and Cady teach that the claimed amounts of the isoxazoline compounds were known in the art and it would have been obvious to one skilled in the art to look towards the teachings of Lehay and Cady for the amounts of the isoxazoline compound. “The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.” In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969). See MPEP 2144.05.
Faassen teaches it was known in the art that particle size distribution affects the release of the drug and that smaller particle size leads to burst release whereas larger particle size needs to be chosen if a long lasting effect is desired. Thus, it would have been obvious to one skilled in the art to manipulate the particle size distribution or the thickness of the isoxazoline compound taught by Lehay to determine the optimal particle size for the desired release rate.
With respect to the claimed mechanical resiliency, the copending application expressly teaches the claimed fluralaner compound and its particle size and thus the same fluralaner compound as claimed would necessarily have the same properties with regards to particle size relationship with mechanical resiliency.
Further, it would have been obvious to one skilled in the art to manipulate the amount of the carboxymethyl cellulose and determine an amount that would provide an optimal dispersion of the suspension because carboxymethyl cellulose is taught by the prior art to be used as a dispersing agent. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here 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." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
From the combined teaching of the cited reference, one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made.
This is a provisional nonstatutory double patenting rejection.
Claims 1-2, 4, 6-14, 21 and 25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 8-13 and 17-18 of copending Application No. 17/606,262 (USPGPUB NO. US20220296564A1) in view of Lehay et al. (WO 2015/091898 A1; Jun. 25, 2015), Cady et al. (US 2016/0256442A1; Sep. 8, 2016) (Cited in IDS filed 8/13/2020) and Wang et al. (WO 2008/030385 A2; Mar. 13, 2008).
The ‘262 application claims an injectable composition comprising moxidectin and particles of an isoxazoline compound, wherein the moxidectin and isoxazoline compound particles are suspended in an aqueous carrier. The composition comprises a suspending agent such as sodium carboxymethyl cellulose. The isoxazoline compound particles have a particles size distribution of from 75 micron to 150 micron. Isoxazoline compound comprises fluralaner. Isoxazoline particles have a thickness greater than 10 micrometer.
The ‘262 application does not claim the amount of the isoxazoline compound. However, this deficiency is cured by Lehay and Cady.
As discussed supra, Lehay teaches the isoxazoline compound is fluralaner in the amount of between 1.5mg/ml and 100 mg/ml (Claims 2 and 3). The amount of fluralener taught by Lehay equates to 0.15% to 10% w/v, which overlaps the amounts recited in instant claims 6 and 8.
As discussed supra, Cady discloses fluralaner as the isoxazoline compound (claim 10). It also teaches the composition comprising about 15% to about 40% of an isoxazoline compound (Para 0240) which overlaps the amount recited in instant claim 7.
The ‘262 application also does not claim the amount of moxidectin. However, this deficiency is cured by Wang.
As discussed supra, Wang teaches formulations for the control of parasites in animals (Abstract). It teaches the formulation comprises moxidectin in an amount of about 0.05% to about 10% which overlaps the amount recited in the instant claims.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have modified ‘262 to incorporate the teachings of Lehay and Cady and include an amount of fluralaner taught by Lehay and Cady in the ‘262 composition. One would have been motivated to do so because ‘262 is silent on the amount of isoxazoline compound and Lehay and Cady teach that the claimed amounts of the isoxazoline compounds were known in the art and it would have been obvious to one skilled in the art to look towards the teachings of Lehay and Cady for the amounts of the isoxazoline compound. “The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.” In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969). See MPEP 2144.05.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have modified ‘262 to incorporate the teachings of Wang and include an amount of moxidectin taught by Wang in the ‘262 composition. One would have been motivated to do so because ‘262 is silent on the amount of moxidectin compound and Wang teaches that the claimed amounts of the moxidectin to control parasites were known in the art and it would have been obvious to one skilled in the art to look towards the teachings of Wang for the amounts of moxidectin. “The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.” In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969). See MPEP 2144.05.
With respect to the claimed mechanical resiliency, the copending application expressly teaches the claimed fluralaner compound and its particle size and thus the same fluralaner compound as claimed would necessarily have the same properties with regards to particle size relationship with mechanical resiliency.
Further, it would have been obvious to one skilled in the art to manipulate the amount of the carboxymethyl cellulose and determine an amount that would provide an optimal dispersion of the suspension because carboxymethyl cellulose is taught by the prior art to be used as a dispersing agent. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here 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." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
From the combined teaching of the cited reference, one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made.
This is a provisional nonstatutory double patenting rejection.
Claims 1-2, 4, 6-8 and 21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 11858904B2 in view of Lehay et al. (WO 2015/091898 A1; Jun. 25, 2015), Cady et al. (US 2016/0256442A1; Sep. 8, 2016) and Faassen et al. (US 8,658,687; Feb. 25, 2014).
‘904 patent claims an isoxazoline compound particle composition comprising particles having a volume weighted particle size distribution (d50) as measured by a static light scattering instrument of between 50 and 150 μm and with a thickness of greater than 10 μm, as measured by scanning electron microscopy (SEM) wherein, the volume weighted particle size distribution (d50) as measured by a static light scattering instrument of the particles does not decrease by more than 40% when the mechanical resiliency as measured by a pressure titration is increased from 1 to 3 bar dispersion pressure, wherein the isoxazoline compound is fluralaner. The particle size distribution (d50) of the particles does not decrease by more than 35% from 1 to 3 bar dispersion pressure. The volume weighted particle size distribution (d50) as measured by a static light scattering instrument is between 75 and 120 μm. The thickness is greater than 20 μm as measured by scanning electron microscopy (SEM).
‘904 patent does not teach the isoxazoline compound is in suspension and composition comprising a suspending agent. ‘904 also does not teach the amount of isoxazoline compound. However, Lehay, Cady and Faassen cure these deficiencies.
As disucussed supra, Lehay throughout the reference teaches a composition comprising isoxazoline compound and the use of the composition to treat or prevent parasite infestation of animals (Abstract). Particularly, Lehay teaches a pharmaceutical composition comprising an isoxazoline compound of formula I and a pharmaceutically acceptable carrier (Claim 1). It teaches the isoxazoline compound is fluralaner in the amount of between 1.5mg/ml and 100 mg/ml (Claims 2 and 3). The amount of fluralener taught by Lehay equates to 0.15% to 10% w/v, which overlaps the amounts recited in instant claims 6 and 8. The reference discloses that the composition according to the invention can be in the form of an aqueous suspension (Page 19, lines 27-29), which would include having a suspending agent.
As discussed supra, Cady discloses fluralaner as the isoxazoline compound (claim 10). It also teaches the composition comprising about 15% to about 40% of an isoxazoline compound (Para 0240) which overlaps the amount recited in instant claim 7.
As discussed supra, Faassen teaches using carboxymethyl cellulose as dispersing agent in the suspension formulations (col. 12, line 66 to col. 13, line 2).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have modified ‘904 to incorporate the teachings of Lehay and Cady and include an amount of fluralaner taught by Lehay and Cady in the ‘904 composition. One would have been motivated to do so because ‘904 is silent on the amount of isoxazoline compound and Lehay and Cady teach that the claimed amounts of the isoxazoline compounds were known in the art and it would have been obvious to one skilled in the art to look towards the teachings of Lehay and Cady for the amounts of the isoxazoline compound. “The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.” In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969). See MPEP 2144.05.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have modified ‘904 to incorporate the teachings of Lehay and Faassen and include isoxazoline compound in suspension comprising a suspending agent such carboxymethyl cellulose. One would have been motivated to do so because both Lehay and ‘904 teach compositions comprising the isoxazoline compound and Lehay teaches that compositions comprising such compound can be made in the form of a suspension and thus, one skilled in the art would have readily envision making a suspension based on the type of administration (e.g., a suspension if an oral or an injection formulation was desired) using carboxymethyl cellulose as dispersing agent in the suspension formulations.
Further, it would have been obvious to one skilled in the art to manipulate the amount of the carboxymethyl cellulose and determine an amount that would provide an optimal dispersion of the suspension because carboxymethyl cellulose is taught by the prior art to be used as a dispersing agent. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here 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." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
From the combined teaching of the cited reference, one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Claims 1-2, 4, 6-8 and 21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims of copending Application No. 18/510,718 in view of Lehay et al. (WO 2015/091898 A1; Jun. 25, 2015), Cady et al. (US 2016/0256442A1; Sep. 8, 2016) and Faassen et al. (US 8,658,687; Feb. 25, 2014).
‘718 claims an isoxazoline compound particle composition comprising particles having a volume weighted particle size distribution (d50) as measured by a static light scattering instrument of between 50 and 150 μm and with a thickness of greater than 10 μm, as measured by scanning electron microscopy (SEM) wherein, the volume weighted particle size distribution (d50) as measured by a static light scattering instrument of the particles does not decrease by more than 40% when the mechanical resiliency as measured by a pressure titration is increased from 1 to 3 bar dispersion pressure, wherein the isoxazoline compound is fluralaner. The particle size distribution (d50) of the particles does not decrease by more than 35% from 1 to 3 bar dispersion pressure. The volume weighted particle size distribution (d50) as measured by a static light scattering instrument is between 75 and 120 μm.
‘718 does not teach the isoxazoline compound is in suspension and composition comprising a suspending agent. ‘718 also does not teach the amount of isoxazoline compound. However, Lehay, Faassen and Cady cure these deficiencies.
As disucussed supra, Lehay throughout the reference teaches a composition comprising isoxazoline compound and the use of the composition to treat or prevent parasite infestation of animals (Abstract). Particularly, Lehay teaches a pharmaceutical composition comprising an isoxazoline compound of formula I and a pharmaceutically acceptable carrier (Claim 1). It teaches the isoxazoline compound is fluralaner in the amount of between 1.5mg/ml and 100 mg/ml (Claims 2 and 3). The amount of fluralener taught by Lehay equates to 0.15% to 10% w/v, which overlaps the amounts recited in instant claims 6 and 8. The reference discloses that the composition according to the invention can be in the form of an aqueous suspension (Page 19, lines 27-29), which would include having a suspending agent.
As discussed supra, Cady discloses fluralaner as the isoxazoline compound (claim 10). It also teaches the composition comprising about 15% to about 40% of an isoxazoline compound (Para 0240) which overlaps the amount recited in instant claim 7.
As discussed supra, Faassen teaches using carboxymethyl cellulose as dispersing agent in the suspension formulations (col. 12, line 66 to col. 13, line 2).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have modified ‘718 to incorporate the teachings of Lehay and Cady and include an amount of fluralaner taught by Lehay and Cady in the ‘718 composition. One would have been motivated to do so because ‘718 is silent on the amount of isoxazoline compound and Lehay and Cady teach that the claimed amounts of the isoxazoline compounds were known in the art and it would have been obvious to one skilled in the art to look towards the teachings of Lehay and Cady for the amounts of the isoxazoline compound. “The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.” In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969). See MPEP 2144.05.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have modified ‘718 to incorporate the teachings of Lehay and Faassen and include isoxazoline compound in suspension comprising a suspending agent such as carboxymethyl cellulose. One would have been motivated to do so because both Lehay and ‘718 teach compositions comprising the isoxazoline compound and Lehay teaches that compositions comprising such compound can be made in the form of a suspension and thus, one skilled in the art would have readily envision making a suspension based on the type of administration (e.g., a suspension if an oral or an injection formulation was desired) using carboxymethyl cellulose as dispersing agent in the suspension formulations.
Further, it would have been obvious to one skilled in the art to manipulate the amount of the carboxymethyl cellulose and determine an amount that would provide an optimal dispersion of the suspension because carboxymethyl cellulose is taught by the prior art to be used as a dispersing agent. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here 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." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
From the combined teaching of the cited reference, one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Response to Arguments
Applicant's arguments filed 3/11/2026 with respect to the double patenting rejections have been fully considered but they are not persuasive.
Regarding double patenting rejection of application 17999024 and 17606262, applicant argued that the rejection is improper as the reference applications are later filed applications and later filed, later expiring patent may not serve as a non-statutory double patenting reference.
In response, applicant’s attention is respectfully drawn to MPEP 1490 which states that “If a provisional nonstatutory double patenting rejection is the only rejection remaining in an application having the earlier patent term filing date, the examiner should withdraw the rejection in the application having the earlier patent term filing date and permit that application to issue as a patent, thereby converting the provisional nonstatutory double patenting rejection in the other application into a nonstatutory double patenting rejection upon issuance of the patent”. Since the double patenting rejections in the present application (earlier filed application) are not the only rejections remaining, the double patenting rejections over applications 17999024 and 17606262 are maintained.
Regarding double patenting rejection over US11858904B2, applicant argued that Lehay teaches the composition is administered via oral route in a unit dosage form such as suspension and that this does not teach an injectable composition of any kind and no teaching of NaCMC.
In response, while Lehay does not exemplify parenteral formulations and particularly suspensions, Lehay does teach the composition may be administered parenterally and also teaches the composition may be a suspension (page 19). Thus, it would have been obvious to one skilled in the art to change the administration route from oral to parenteral wherein the composition is a suspension since Lehay clearly suggests parenteral route and a suspension composition is within the scope of the invention. Further, as discussed supra, Faassen teaches NaCMC as suspending agent can be added to suspension formulations.
Regarding double patenting rejection over application 18510715, applicant argued the claims are directed to processes to make isoxazoline particles and are a separate invention from the injectable composition of the subject claims.
In response, while the ‘715 claims are directed to a process of making isoxazolin particles, the resulting composition claimed in ‘715 in view of the cited references reads on the claimed composition. Further, the present application is not a divisional of ‘715 application and therefore, the rejection is appropriate.
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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/A.S/Examiner, Art Unit 1616
/SUE X LIU/Supervisory Patent Examiner, Art Unit 1616
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