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
Status of claims
The amendment filed on April 21, 2026 is acknowledged. Claims 2-3, 5-8, 10, 12, 14-15, 17, and 19-21 have been canceled and claims 11, 13, 16, 18, and 25-26 have been withdrawn.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, 9, and 22-24 are under examination in the instant office action.
Applicants' arguments, filed on April 21, 2026, have been fully considered but they are not found to be persuasive or moot in view of a new ground of rejection necessitated by the amendments (newly added limitations and deleting a limitation (6 months deleted)). Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.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.
The word, “microfiliare” in line 5 appears to be misspelled. It should be corrected to --microfilariae--.
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, 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 Prichard et al. (Drugs and Drug Resistance 2:134–153, 2012; cited in the IDS filed on 8/6/2021) and US 2013/0137669 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 the amended claim 1 and claim 22-23.
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 avermectin such as ivermectin which is increased by at least 15 % as compared to the EC50 value of the wild-type as recited in the amended claim 1.
As to the limitation: “the effective amount of moxidectin promotes attachment of microfilariae 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.
McTier et al. are silent about the subject being infected with microfilariae of D. immitis which are resistant to an avermectin that was previously administered to the subject to treat microfilariae of D. immitis.
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).
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 a subject being infected with microfilariae of D. immitis which are resistant to an avermectin that was previously administered to the subject to treat D. immitis microfilariae infection because McTier et al. teaches that moxidectin is effective for killing microfilariae (MF) 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 avermectin on the reasonable expectation success.
Also, McTier et al. does not specifically disclose administration frequency as amended.
However, US 2013/0137669 teaches and suggests that macrocyclic lactones could be used monthly to suppress reproduction in adult worms and remove microfilarial (mf) stages, thereby reducing transmission and gradually causing the attrition of adult worms ([0023]). Thus, 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. Also, the skilled artisan would have been motivated to use moxidectin as needed basis for desired therapeutic effects. 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.
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.”)
Response to Applicant’s arguments
Applicants argued that McTier is limited to resistant adult Dirofilaria immitis and does not teach avermectin-resistant Dirofilaria immitis microfilariae and promoting attachment to leukocytes. Also, Applicant argued that while Prichard mentions Dirofilaria immitis microfilariae in passing, Prichard does not specifically teach that Dirofilaria immitis microfilariae is resistant to avermectin, the effective amount of moxidectin promotes attachment to leukocytes, and the effective amount of moxidectin is enough to give claimed plasma concentration in the subject. In addition, Applicant argued that WO’961 fails to remedy the deficiencies of McTier and Priochard because it does not provide any guidance on treating a Dirofilaria immitis microfilariae infection that resistant to avermectin. Further, Applicant argued that WO’961 would be discouraged from monthly administration. Finally, Applicant argued that while the USPTO relied on inherency to meet the claim elements of the dosage of moxidectin (the effective amount of moxidectin is enough to give claimed plasma concentration in the subject of 0.1-100 nM of moxidectin) nothing in WO ‘961 provides any guidance on how to achieve the effective amount of moxidectin that is enough to give the claimed plasma concentration.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). It is important to note that in an obvious rejection, it is not necessary that one reference addresses any limitation in a particular claim but that the references, when combined, do so. “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious”, the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR v. Teleflex, 127 S.Ct. 1727, 1741 (2007). The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742. The motivation to combine may be implicit and may be found in the knowledge of one of ordinary skill in the art, or, in some cases, from the nature of the problem to be solved. Id. at 1366, 80 USPQ2d at 1649. “[A]n implicit motivation to combine exists not only when a suggestion may be gleaned from the prior art as a whole, but when the improvement’ is technology-independent and the combination of references results in a product or process that is more desirable, for example because it is stronger, cheaper, cleaner, faster, lighter, smaller, more durable, or more efficient. Because the desire to enhance commercial opportunities by improving a product or process is universal-and even common-sensical-we have held that there exists in these situations a motivation to combine prior art references even absent any hint of suggestion in the references themselves. In such situations, the proper question is whether the ordinary artisan possesses knowledge and skills rendering him capable of combining the prior art references.” Id. at 1368, 80 USPQ2d at 1651.
Consistent with this reasoning, it would have been prima facie obvious to one of ordinary skill in the art to use moxidectin for treating infection of D. immitis microfilariae, which is resistant to an avermectin such as ivermectin because McTier et al. teaches that moxidectin is effective for killing microfilariae of D. immitis resistant to other ML such as ivermectin. Also, Prichard et al. teach that in many cases when resistance to avermectins is noticed, Moxidectin 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 avermectin on the reasonable expectation success. The examiner recognizes that obviousness can only be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988) and In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992). It is also noted that "The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain." In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) (quoting In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968)).
Also, on the contrary to Applicants’ assertion, McTier et al. do teach administering PH 6 (moxidectin) at 0.17 mg/kg to MF (microfilariae)-positive dogs infected with the isolate of D. immitis (ZoeMo-2012) (see p48-49, Design and Treatment sections) and disclose microfilaricidal effects of PH 6 on microfilariae obtained from the blood of those dogs. The isolate of D. immitis (ZoeMo-2012) is confirmed to be resistant to macrocyclic lactones such as ivermectin and was taken from the same parent dog from which the original JYD-34 isolate had been taken (see abstract and p48, col 2, para 2). Thus, the dogs have infection of D. immitis microfilariae which is produced from the resistant isolate of D. immitis (ZoeMo-2012). Since the microfilariae is derived from avermectin-resistant isolate of D. immitis, McTier et al. do teach avermectin-resistant Dirofilaria immitis microfilariae. This is further evidenced by the instant specification that the resistant Dirofilaria immitis microfilariae was obtained from the blood of dogs that was infected with isolate of resistant D. immitis (adults) (see [0069] and [0070]). In addition, 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).
In response to the argument regarding “monthly administration”, the examiner points out that the rejection has been modified as necessitated by amendment and “monthly administration” has been addressed by the modified rejection as stated above.
As to the effective amount of moxidectin that is enough to give claimed plasma concentration in the subject, McTier et al. disclose administering a single SC dose of PH 6 (Proheart 6, 0.17 mg/kg) decreased MF counts gradually. WO 2019/101961 was cited as evidentiary reference because WO 2019/101961 discloses administering the same Proheart 6 at the same dose (0.17 mg/kg) to a dog and discloses that such administration resulted in a plasma concentration of about 2 ng/ml of moxidectin in the subject (see 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 taught by McTier et al. falls within the range of the effective amount that is enough to give claimed plasma concentration of moxidectin recited in the amended claim 1 and claim 22-23. This is not based on the inherency but based on the evidentiary reference.
As to the limitation: “the effective amount of moxidectin promotes attachment of microfilariae to leukocytes”, the reference teaches administering the same compound (moxidectin) at the same dose to the same subject (dog), thus administering moxidectin as taught by McTier et al. necessarily has the claimed activity. It should be noted that products of identical chemical composition cannot exert mutually exclusive properties when administered under the same circumstances or, in the present case, the same host. See MPEP §2112.
Applicants are advised that In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) states: "Where, as here, the claimed and prior art product is identical or substantially identical, or is produced by an identical or substantially identical process, the PTO can require an applicant to prove that the prior art product does not necessarily or inherently possess the characteristics of his claimed product ........ Whether the rejection is based on 'inherency' under 35 USC 102, on 'prima facie obviousness' under 35 USC 103, jointly or alternatively, the burden of proof is the same, and its fairness is evidenced by the PTO's inability to manufacture products or to obtain and compare prior art products [footnote omitted]." Applicant did not provide any evidence that administering moxidectin as taught by McTier et al. does not result in “promoting attachment of microfilariae to leukocytes as claimed.
For the foregoing reasons, Applicant’s arguments have not been found to be persuasive.
Conclusion
No claims are allowed.
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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BONG-SOOK BAEK whose telephone number is 571-270-5863. The examiner can normally be reached 9:00AM-6:00PM Monday-Friday.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bethany Barham can be reached on 571-272-6175. The fax phone number for the organization where this application or proceeding is assigned is (571) 273-8300.
Information regarding the status of an application may be obtained from Patent Center. Status information for published applications may be obtained from Patent Center. Status information for unpublished applications is available through Patent Center for authorized users only. Should you have questions about access to Patent Center, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) Form at https://www.uspto.gov/patents/uspto-automated- interview-request-air-form.
/BONG-SOOK BAEK/Primary Examiner, Art Unit 1611
Prosecution Insights