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 .
DETAILED ACTION
A request for continued examination under 37 C.F.R. 1.114, including the fee set forth in 37 C.F.R. 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 C.F.R. 1.114, and the fee set forth in 37 C.F.R. 1.17(e) has been timely paid, the finality of the previous Office Action has been withdrawn pursuant to 37 C.F.R. 1.114. Applicant’s submission filed Nov. 21, 2025 has been received and entered into the present application.
Status of claims
The amendment filed on Nov. 21, 2025 is acknowledged. Claims 2-3, 7, 10, 12, 14-15, 17, and 19-21 have been canceled and claims 11, 13, 16, 18, and 25-26 have been withdrawn. Claims 1, 4-6, 8-9, and 22-24 are under examination in the instant office action.
Applicants' arguments, filed on Nov. 21, 2025, have been fully considered but they are moot in view of a new ground of rejection necessitated by the amendments (newly added limitations). Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Objections
Claim 1 is objected to because of the following informalities: typographical errors. In the recitation, “the Dirofilaria immitis microfilariae is resistant to is an avermectin” in lines 4-5, the word “is” before “an avermectin” should be deleted.
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 5 and 6 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 pre-AIA the applicant regards as the invention.
Claims 5-6 as amended recites the limitation "at least one other macrocyclic lactone" in lines 2-3. There is a lack of antecedent basis for this limitation in the claim because the amended claim 1 no longer recites “at least one other macrocyclic lactone”. It is also confusing whether it is intended to refer to “avermectin” only, or any other macrocyclic lactone. Clarification is required. For the examination purpose, it is interpreted to refer to “avermectin” only.
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 1, 4-5, 9, and 22-24 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by McTier et al. (The Author(s) Parasites & Vectors 2017, 10(Suppl 2):485, p47-52; cited in the IDS filed on 8/26/2021) as evidenced by WO 2019/101961 (prior art of record).
McTier et al. disclose the study regarding the effects of ProHeart® 6 (PH 6; Zoetis) and ProHeart® SR-12 (PH 12; Zoetis) on reduction of microfilariae (MF) of Dirofilaria Immitis (heartworm) in dogs experimentally inoculated with an isolate of Dirofilaria Immitis (ZoeMo-2012) confirmed to be resistant to MLs, wherein both PH 6 and PH 12 were highly effective in reducing the MF levels of the confirmed ML-resistant heartworm isolate following a single dose (title, abstract and p48, Conclusion). McTier et al. further disclose that the dogs received a subcutaneous injection (parenteral administration) of either saline (placebo-treated control, 6 dogs), PH 6 (0.17 mg/kg, 6 dogs), PH 12 (0.5 mg/kg, 5 dogs) or a single oral dose of moxidectin powder in a gelatin capsule (0.25 mg/kg, 6 dogs) (abstract). Also, McTier et al. discloses that the dogs infected with the ML-resistant isolate of D. immitis are positive for MF (microfilariae) (p48, col 2, para 2-3). Thus, the dogs have D. immitis microfilariae infection. McTier et al. teach that reducing the availability of resistant microfilariae in nature for transmission to other competent hosts would be beneficial in reducing the spread of resistant heartworms (p48, col 1, para 2).
ProHeart® 6 (PH 6; Zoetis) is a slow-release formulation of subcutaneously injected moxidectin-impregnated lipid microspheres as evidenced by WO 2019/101961 (p3, lines 31-34). Also, the administration of PH 6 at the dose of 0.17 mg/kg appears to results in a plasma concentration of about 2 ng/ml of moxidectin in the subject as evidenced by WO 2019/101961 (p25, Example 11 and Fig. 1). The plasma concentration of 2 ng/ml of moxidectin (MW: 640 g/mol) is about 3 nM. Thus, the dose of 0.17 mg/kg falls within the range of the effective amount enough to give a plasma concentration recited in claims 1 and 22-23 as claimed.
McTier et al. disclose that the isolate of D. immitis (ZoeMo-2012) was taken from the same parent dog from which the original JYD-34 isolate had been taken (p48, col 2, para 2) and there was lack of efficacy of monthly preventive products containing selamectin, milbemycin oxime and ivermectina against the JYD-34 and this suggests that the isolate is resistant to approved doses of those MLs (p50, col 2, last para-p51, col 1, para 2). This lack of efficacy implicitly teaches that the resistant D. immitis exhibits an EC50 value of the at least one other macrocyclic lactone which is increased by at least 15 % as compared to the EC50 value of the wild-type nematode as recited in claim 5.
As to the limitation: “the effective amount of moxidectin promotes attachment of microfiliare to leukocytes”, it is an intended result of the active method step, and as such is non-limiting since the language does not result in manipulative difference in steps of claims. The reference teaches administering the same compound at the same dose to the same patient, thus administering the compound as taught by the prior art necessarily has the claimed activity. “[T]he 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.” Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir.1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). “[N]ewly discovered results of known processes directed to the same purpose are not patentable." Bristol-Myers Squibb, 246 F.3d at 1376. Also, see In re Fitzgerald, 619 F.2d 67, 205 USPQ 594 (CCPA 1980) (a case indicating that the burden of proof can be shifted to the applicant to show that the subject matter of the prior art does not possess the characteristic relied on whether the rejection is based on inherency under 35 U.S.C.102 or obviousness under 35 U.S.C. 103.
As such, the instant claims are anticipated by McTier et al.
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 of this title, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 1, 4-6, 8-9, and 22-24 are rejected under 35 U.S.C. 103 as being unpatentable over in McTier et al. (The Author(s) Parasites & Vectors 2017, 10(Suppl 2):485, p47-52) in view of WO 2019/101961 (prior art of record) and Prichard et al. (Drugs and Drug Resistance 2:134–153, 2012; cited in the IDS filed on 8/6/2021).
The teachings of McTier et al. and WO 2019/101961 et al. as applied supra are herein applied for the same teachings in their entirety.
Prichard et al. teach the long-acting moxidectin (MOX) injectable preparations ProHeart®6 (and ProHeart®12) provide 6 months (and 12 months) of protection against heartworm disease by Dirofilaria immitis and IVM (at 50 μg/kg) and MO are also known to kill microfilariae of D. immitis (p137-138, 4.4). Prichard et al. further teach that resistance to the avermectins has become widespread in parasites of some hosts (abstract). Prichard et al. also teach while there is some degree of cross-resistance between the avermectins and MOX, avermectin resistance and MOX resistance are not identical, and in many cases when resistance to avermectins is noticed, MOX produces a higher efficacy and quite often is fully effective at recommended dose rates (abstract). In addition, Prichard et al. teach that because of exceptionally high potency and safety of MOX, it is used in dose ranges varying between 3 μg/kg (e.g., ProHeart® for dogs) to 2.5 mg/kg (e.g., Advantage Multi® for dogs) (p137, col 1, para 2). Prichard et al. disclose that different doses are used for different administration routes and species, wherein the i.v. (intravenous injection) dose is 0.07 mg/kg (70 µg/kg) for cattle, Sc (subcutaneous) dose is 0.2 mg/kg for cattle, sheep and goat, and oral doses are 0.25 or 0.5 mg/kg for dog or human (p140, Table 1).
McTier et al. are silent about the subject being infected with microfilariae of D. immitis which are resistant to at least one other macrocyclic lactone anthelmintic that was previously administered to the subject to treat microfilariae of D. immitis. However, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use moxidectin for such subject because McTier et al. teaches that moxidectin is effective for treating infection with microfilariae of D. immitis resistant to other macrocyclic lactone such as ivermectin. Also, Prichard et al. teach that in many cases when resistance to avermectins is noticed, MOX produces a higher efficacy and quite often is fully effective at recommended dose rates. Thus, the skilled artisan would have been motivated to use moxidectin as alternative treatment for those who have developed resistance due to previous treatment of other macrocyclic lactones on the reasonable expectation success.
As to claim 8, McTier et al. does not specifically disclose administration frequency.
However, WO 2019/101961 teaches topically administering every 3 to 9 months to said non-human mammal a veterinary or pharmaceutical composition comprising moxidectin for treatment and/or prevention of parasites infestations wherein the parasitic infestation is caused by nematodes such as Dirofilaria immitis (abstract, p1, lines 9-11, and claims 1 and 5-6). Also, WO 2019/101961 teaches the use of a long acting (at least months) composition of which one single application is sufficient and with optimized plasmatic concentration of drug to minimize long term toxicity issue in animal and discloses a 3, 4, 5, 6, 7, 8, or 9 months long-acting pharmaceutical composition comprising moxidectin, which can be administered every 3 to 9 months (p5, lines 17-21 and p15, lines 12-26). WO 2019/101961 (p3, lines 31-34) discloses that the administration of PH 6 at the dose of 0.17 mg/kg results in a plasma concentration of about 2 ng/ml of moxidectin in the subject (p25, Example 11 and Fig. 1). The plasma concentration of 2 ng/ml of moxidectin (MW: 640 g/mol) is about 3 nM. The plasma concentration falls within the claimed range.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to arrive at the claimed administration frequency through optimization depending on the type of formulation used because it was already known in the art that the long-acting composition comprising moxidectin can be administered every 3 to 9 month including every 6 months for treating infection with the same heartworms (Dirofilaria immitis) as evidenced by WO 2019/101961. Also, the skilled artisan would have been motivated to use the long-acting formulation comprising moxidectin for minimizing long term toxicity issue in animal. In addition, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to optimize an effective amount of MOX for obtaining a plasma concentration sufficient to provide therapeutic effects based on the teachings of the prior art in combination. Those of ordinary skill in the art would have readily optimized administration regimen as determined by good medical practice, the clinical condition of the individual patient, and patient' s response to initial administration, and depending on which types of dosage forms (short-acting or long-acting) and administration routes (oral, parenteral, topical, etc.) are used. Also, 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).
In addition, it is well-established that merely selecting proportions and ranges is not patentable absent a showing of criticality. In re Becket, 33 USPQ 33; In re Russell, 169 USPQ 426. “[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); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“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.”)
Conclusion
No claims are allowed.
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/BONG-SOOK BAEK/Primary Examiner, Art Unit 1611