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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 03/09/2026 has been entered.
Election/Restrictions
Applicants' election with traverse of Group II (i.e., claims 17-18, drawn to a method of controlling parasitic mites and/or ticks, particularly in a bee colony, comprising delivering an acaricide to the bee colony, the acaricide comprising a peptide analog or peptidomimetic of proctolin), in the reply filed on 07/01/2025 is acknowledged. Additionally, Applicants’ election of Species A (i.e., Single and specific peptide analog or peptidomimetic of proctolin); Applicants’ election: peptide of Ac-2441: Ac-R[Phe(4-F)]L[HyP]T (SEQ ID NO: 35), in the reply filed on 07/01/2025 is also acknowledged.
However, the traversal of Group II is on the ground(s) that the Brunkow and Park disclosures are disqualified as prior art because a Declaration under Rule 130 by Yoonseong Park, PhD, an inventor of the instant application is a named author of the Brunkow et al. reference, which was published in December 2018. Additionally, the Declarant is the sole author of the Park reference published in May 2019 (see Remarks, filed on 07/01/2025, pg. 5). Applicants also asset that the instant application claims priority to U.S. Provisional Application No. 62/904,463 filed on 09/23/2019, which is less than 12 months after the publication of the cited prior art (i.e., Brunkow et al. 2018 and Park 2019) (see Remarks, filed on 07/01/2025, pg. 5).
This is not found persuasive because the grace period disclosure by inventor or obtained from the inventor does not pertain to the requirement for unity of invention. However, even if the “Grace Period Disclosure by Inventor or Obtained from Inventor” exception applied to the cited art (i.e., Brunkow et al. 2018 and Park 2019); the requirement for unity of invention is still deemed proper, in light of the art discussed below.
The requirement is still deemed proper and is therefore made FINAL.
Please note for purposes of compact prosecution, the election of species is modified only to the extent of examining additional species (i.e., SEQ ID NOs: 5, 7-8, 27, 29 and 37). Otherwise the election of species requirement is still retained.
Status of Claims
Claims 1-20 were originally filed and amended on 03/23/2022. The amendment cancelled claim 20, and amended claims 15 and 17.
The amendment filed on 11/11/2025, cancelled claims 1-16, added new claims 21-26 and amended claims 17-18.
The amendment filed on 03/06/2026, amended claim 17.
Claims 17-18 and 21-26 are currently pending and under consideration.
Priority
The present application claims the benefit under 35 U.S.C 119 (e) to U.S. Provisional Application No. 62/904,436 September 23rd 2019. Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C 119 (e) or under 35 U.S.C 120, 121, or 365 (c ) is acknowledged.
The present application also claims status as a 371 (National Stage) of PCT/US2020/052134 filed September 23rd 2020.
Claim Interpretation
For purposes of applying prior art, the claim scope has been interpreted as set forth below per the guidance set forth at MPEP § 2111. If Applicant disputes any interpretation set forth below, Applicant is invited to unambiguously identify any alleged misinterpretations or specialized definitions in the subsequent response to the instant action. Applicant is advised that a specialized definition should be properly supported and specifically identified (see, e.g., MPEP § 2111.01(IV), describing how Applicant may act as their own lexicographer).
For claim 17, regarding the scope of the “acaricide comprising a peptide analog or peptidomimetic according to claim 1”, it is noted that the instant specification does not define what constitutes a “peptide analog” or “peptidomimetic”. Rather, the instant specification teaches that the peptide analog or peptidomimetic comprises one or two amino acid residue substitutions or insertions (see pg. 2, lines 25-26). Pursuant to MPEP 2111.01, under a broadest reasonable interpretation, words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification. The plain meaning of a term means the ordinary and customary meaning given to the term by those of ordinary skill in the art at the time of the invention. Merriam’s Webster dictionary defines “analog” as something that is similar or comparable to something else either in general or in some specific detail (see Merriam Webster, “Analog”, available online at https://www.merriam-webster.com/dictionary/analog, accessed on 08/07/2025). As such, the Examiner is interpreting the scope of “peptide analog” as a modified version of a naturally occurring peptide with one or two amino acid substitutions or insertions.
With respect to the acaricide comprising a “peptide analog” or “peptidomimetic”; both the analog and the peptidomimetic comprise the same structural limitation, i.e., one or two amino acid residue substitutions or insertions. Peptidomimetics are generally defined as compounds whose essential elements (pharmacophore) mimic a natural peptide or protein in 3D space, and which retain the ability to interact with the biological target and produce the same biological effect (see Vagner et al., 2008, pg. 1, Introduction). Therefore, in order to advance prosecution, the Examiner is interpreting a peptide analog and a peptidomimetic as a peptide with one or two amino acid residue substitutions or insertions.
Additionally, with respect to the acaricide, it is noted that claim 17 does not recite a distinction between the analog or the peptidomimetic, and given that both an analog of SEQ ID NO: 1 and a peptidomimetic of SEQ ID NO: 1 comprise the same structural limitation (i.e., one or two amino acid residue substitutions or insertions), and combined with the pre-existing knowledge in the art regarding proctolin (i.e., instant SEQ ID NO: 1) analogs modified at positions 1-5 (see Konopinska. 1996, Tables 1, 3 and 4.), an ordinary skilled artisan would conclude that the Applicant was in possession of the claimed genus at the time the application was filed.
Response to Arguments
1. Applicants’ arguments, see Remarks, filed 03/06/2026, with respect to the objection to claim 17; have been fully considered and are persuasive. The objection to claim 17 has been withdrawn.
2. Applicants’ arguments, see Remarks, filed 03/06/2026, with respect to 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement (i.e., new matter); have been fully considered and are persuasive. The 35 U.S.C. 112(a) rejection of claims 17-18 and 21-26 has been withdrawn.
3. Applicants’ arguments, see Remarks, filed 03/06/2026, with respect to 35 U.S.C. 103 as being unpatentable over US 2013/0224275 A1 Pub Date: Aug. 29, 2013 (herein after “Storm”), as evidenced by The Health Canada Pest Management Regulatory Agency- Registration Decision “Thymol”, 2016, pp. 1-6 (herein after “HCPMRA”), in view of Konopinska. D., J. Peptide Res. 49, 1997, pp. 457-466 (herein after “Konopinska”), Konopinska et al., Bulletin of the Polish Academy of Sciences Chemistry, Vol. 41, No. 1, 1993, pp 27-39 (herein after “Konopinska 2”), O’Shea. M., “Neuropeptides in Insects: Possible Leads to New Control Methods” in Approaches to New Leads for Insecticides, 1985, pp. 133-151 (herein after “O’Shea”), Caers et al., Frontiers in Endocrinology, 2012., vol. 3, article 151, pp. 1-30 (herein after “Caers”); and US 4,876,265 Date of Patent: Oct. 24, 1989 (herein after “Schmid”); have been fully considered but are not persuasive. The 35 U.S.C. 103 rejection of claims 17-18 and 21-26 has been maintained.
Maintained/Modified Rejections
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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.
103 - KSR Examples of 'Rationales' Supporting a Conclusion of Obviousness
(Consistent with the "Functional Approach" of Graham)
Further regarding 35 USC 103(a) rejections, the Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 127 S. Ct. 1727, 82 USPQ2d 1385, 1395-97 (2007) (KSR) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham. The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit.
Exemplary rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Note that the list of rationales provided is not intended to be an all-inclusive list. Other rationales to support a conclusion of obviousness may be relied upon by Office personnel.
Also, a reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976).
3. Claims 17-18 and 21-26 are rejected under 35 U.S.C. 103 as being unpatentable over US 2013/0224275 A1 Pub Date: Aug. 29, 2013 (herein after “Storm”), as evidenced by The Health Canada Pest Management Regulatory Agency- Registration Decision “Thymol”, 2016, pp. 1-6 (herein after “HCPMRA”), in view of Konopinska. D., J. Peptide Res. 49, 1997, pp. 457-466 (herein after “Konopinska”), Konopinska et al., Bulletin of the Polish Academy of Sciences Chemistry, Vol. 41, No. 1, 1993, pp 27-39 (herein after “Konopinska 2”), O’Shea. M., “Neuropeptides in Insects: Possible Leads to New Control Methods” in Approaches to New Leads for Insecticides, 1985, pp. 133-151 (herein after “O’Shea”), Caers et al., Frontiers in Endocrinology, 2012., vol. 3, article 151, pp. 1-30 (herein after “Caers”); and US 4,876,265 Date of Patent: Oct. 24, 1989 (herein after “Schmid”).
Regarding claim 17, a method of controlling parasitic mites and/or ticks in a bee colony, comprising delivering a bee-safe acaricide to the bee colony, the acaricide comprising one or more peptide analogs or peptidomimetics having a sequence selected from the group consisting of: Ac-R[Phe(4-NO2)]L[HyP]T (SEQ ID NO: 5); R[β3F]L[HyP]T (SEQ ID NO: 7); R[dY]L[HyP]T (SEQ ID NO: 8); RYL[HyP]T (SEQ ID NO: 27); RYL[Oic]T (SEQ ID NO: 29); Ac-R[Phe(4-F)]L[HyP]T (SEQ ID NO: 35); Ac- R[Phe(4-Cl)]L[HyP]T (SEQ ID NO: 37):
Storm teaches a method of delivering a biologically active chemical agent to an arthropod pest of a bee (see pg. 1, para[0005]). The biologically active agent is selected to have a population controlling action against tracheal mites and/or varroa mites that affect commercial and domestic strains of Apis mellifera species (see pg. 1, para[0009]). Storm adds that the target organism is a parasite of the species Apis mellifera such as Varroa destructor or Acarapis wood (see pg. 2, para[0018]). Thereby constituting a method of controlling parasitic mites in a bee colony as recited in instant claim 17. The arthropod pest such as a mite may be exposed to the biologically active chemical agent prior to egg hatch; during egg hatch; at any stage thereafter; or a combination thereof (see pg. 1, para[0011]). Thereby constituting delivering a bee-safe acaricide to the bee colony as recited in instant claim 17. Storm teaches that the biologically active chemical agent is selected from acaricides (miticites), ovicides active against mite ova, mite growth regulators, essential oils or any combination of two or more thereof (see pg. 2, para[0013]). Preferably, the population of composite carnauba wax particles has as a chemical agent, one that is selected from the group of essential oils: oil of rosemary, cedarwood oil, camphor oil, chamomile oil, menthol or thymol or a combination of thymol and at least one other oil thereof (see pg. 2, para[0013]). Preferably, the biologically active chemical agent of use in the invention is the essential oil thymol.
As evidenced by HCPMRA, Varroa mites are more sensitive to thymol than bees; therefore, the thymol vapours are at a high enough concentration to be toxic to varroa mites but are not high enough to harm bees (see HPCMRA, pg. 2, second paragraph). As such, the teachings of Storm read on a method of controlling parasitic mites and/or ticks in a bee colony, comprising delivering a bee-safe acaricide to the bee colony.
However, Storm does not expressly teach or suggest that the acaricide comprises one or more peptide analogs or peptidomimetics having a sequence selected from the group consisting of: Ac-R[Phe(4-NO2)]L[HyP]T (SEQ ID NO: 5); R[03F]L[HyP]T (SEQ ID NO: 7); R[dY]L[HyP]T (SEQ ID NO: 8); RYL[HyP]T (SEQ ID NO: 27); RYL[Oic1T (SEQ ID NO: 29); Ac-R[Phe(4-F)]L[HyP1T (SEQ ID NO: 35); Ac- R[Phe(4-Cl)]L[HyP]T (SEQ ID NO: 37):
Konopinska teaches insect neuropeptide proctolin and its analogues (see pg. 457, Title). Konopinska’s work focuses on numerous studies with the purpose of evaluating its possible insecticidal activity, determine the mechanism of its myotropic action, search for biological effects in vertebrates, investigate its conformation, and examine its structure-function relationship (see pg. 457, right column, last paragraph). Konopinska studied the structure-myotropic activity relationship of proctolin in insects and that structural modification included a consecutive replacement of proctolin native amino acid residues at positions 1, 2, 3, 4 or 5 of the peptide chain by other natural or non-natural amino acids (see pg. 458, left column, paragraph 1). Thereby, constituting wherein the acaricide comprises one or more peptide analogs or peptidomimetics, as recited in instant claim 17.
With respect to Applicants’ elected species of peptide analog or peptidomimetic of proctolin (i.e., Ac-R[Phe(4-F)]L[HyP]T, SEQ ID NO: 35):
Konopinska teaches the significance of particular amino acid residues such as the Arg residue in the N-terminal part of the proctolin chain for myotropic effect in insects (see pg. 458, right column, pg. 458). The N-terminal amino acid (Arg) is required for full intrinsic activity, and that N-terminally substituted proctolin analogues such as Arg0, homo-Arg1 preserved full proctolin myostimulatory properties (see pg. 458, right column, paragraph 2). With respect to the L-Tyrosine2 residue, Konopinska teaches that various structure-activity relationship data reported show the importance of position 2 of the proctolin moiety for its agonistic activity; such as [Phe(p-F)2] which shows agonistic activity in relationship to proctolin (see pg. 460, left column, paragraph 2; pg. 459, Table 2). With respect to the L-Leucine3 residue in proctolin, Konopinska teaches that the leucine at position 3 is situated between a Tyr residue, which plays an important role in cardiotropic activity in insects and a Pro-residue, which is responsible for stabilization of the biologically active proctolin conformation (see pg. 460, right column, last paragraph). Konopinska adds that the Leu residue in position 3 plays an essential role in the hydrophobic interaction of proctolin with its receptor site (see pg. 461, left column, paragraph 1). With respect to L-Proline4; Konopinska teaches that only [Hyp4]-proctolin preserved a weak agonistic proctolin activity, whereas other analogues were inactive in the cardiotropic assay (see pg. 461, right column only paragraph). These results suggest that the presence of Pro-4 in the proctolin molecule is essential for its cardiotropic properties in insects (see pg. 461, right column only paragraph). With respect to L-Threonine5; Konopinska also teaches that among the proctolin analogues modified in position 5, only two analogues [Ala5]and [N-Me-Thr5]-proctolin showed agonistic effects; suggesting that the role of the C-terminal part of the proctolin molecule needs further study (see pg. 461, right column only paragraph, and pg. 462, left column paragraph 1). The myotropic activity of proctolin analogues in insects has focused on contractions of the hindgut of the cockroach P. americana, heartbeat frequency in P. americana or Tenebrio molitor, the oviduct of L. migratoria and foregut contractions of Schistocerca gregaria (see pg. 458, left column, paragraph 2). Therefore an ordinary skilled artisan after reading Konopinska, would be motivated with reasonable expectation of success to modify the proctolin pentapeptide (i.e., RYLPT) in order to arrive at one or more peptide analogues or peptidomimetics having the sequence Ac-R[Phe(4-F)]L[HyP]T where the second position is substituted by Phe(4-F) and the fourth position is substituted by HyP. As such, the teachings of Konopinska read on instant SEQ ID NO: 35.
Additionally, Konopinska 2 teaches proctolin analogues modified in position 4 of the peptide chain and their influence on the heart beat frequency of insects (see pg. 27, Title). Konopinska 2 performed synthesis of a series of analogues modified in position 4 of the proctolin peptide chain represented by the general formula Arg-Tyr-Leu-X-Thr, where X = Hyp (i.e., peptide 1), Hyp (4-0Me) (i.e., peptide 2), Thz (i.e., peptide 3), homo-Pro (i.e., peptide 4), Ach (i.e., peptide 5) and Sar (i.e., peptide 6) (see pg. 27, second paragraph). The proctolin skeleton has been altered so that in place of the native Pro, in position 4 some other amino acid residues containing the pyrrolidine substituted system with 4’ – OH and 4’ - OMe groups (peptide 1 and 2) were introduced (see pg. 27, third paragraph). Konopinska 2 reports that of the two bioassayed compounds [Hyp4]-proctolin (i.e., peptide 1) is the more cardioactive agonist than the pentapeptide comprising homo-Pro ( i.e., peptide 4). Therefore an ordinary skilled artisan after reading Konopinska 2, would have been motivated with reasonable expectation of success to modify the proctolin pentapeptide (i.e., RYLPT) in order to arrive at a peptide analogue or peptidomimetic having the sequence RYL[HyP]T where the fourth position is substituted by HyP in order to arrive at instant SEQ ID NO: 27. As such, the teachings of Konopinska 2 read on instant SEQ ID NO: 27.
With respect to delivering a bee-safe acaricide to the bee colony, as recited in instant claim 17: Caers teaches that proctolin or RYLPT is a myo- and neurostimulatory neuropeptide of which the appearance seems to be restricted to arthropods (see pg. 14, right column, paragraph 2). Proctolin stimulates or potentiates muscle contraction, is cardio-acceleratory and acts as a neurohormone (see pg. 14, right column, paragraph 2). Caers also teaches that the proctolin and/or proctolin receptor gene was found in the genomes of only a few insect species, including T. castaneum, T. molitor, P. humanus, and A. pisum (see pg. 14, right column, paragraph 2). No proctolin gene has been identified in genomes of A. mellifera (i.e., common name Western Honey bee or European Honey bee), where proctolin and its receptor are now considered absent (see pg. 14, right column, paragraph 2). Thus, Caers demonstrates that proctolin would effectively control arthropod populations such mites and ticks that parasitize a bee colony without affecting the bees, because the proctolin gene and its receptor are considered to be absent in the genomes of A. mellifera.
Furthermore, O’Shea teaches that proctolin is not restricted to the cockroach nor to insects (see pg. 135, paragraph 2). It is known to occur in at least six orders of insect; as mentioned in Brown 1975, though curiously it is absent from Lepidoptera (i.e., butterflies and moths) (see pg. 135, paragraph 2). It seems possible, however, that proctolin itself or closely related peptides exist outside the arthropods (see pg. 135, paragraph 2). O’Shea also teaches that the actions of proctolin are diverse and not restricted to the activity that permitted its isolation (see pg. 135, paragraph 3). No longer should proctolin be considered to be only a "gut peptide" (see pg. 135, paragraph 3). Once synthetic proctolin became available it was possible to examine its bioactivities in a variety of preparations (see pg. 135, paragraph 3). For example, proctolin causes contraction of insect skeletal muscle and induces a myogenic rhythm of contraction and relaxation (see pg. 135, paragraph 3). Later it was demonstrated that proctolin acts on the insect heart; in addition there is now evidence of actions of proctolin on neurons of the insect CNS (see pg. 135, paragraph 3). Moreover, O’Shea teaches that proctolin initiates a long-lasting contracture without depolarizing the muscle and that proctolin is involved as a co-transmitter in the process of skeletal neuromuscular transmission, its actions being mediated locally rather than hormonally (see pg. 136, paragraph 1). As such, the teachings of O’Shea when combined with the teachings of Caers are suggestive of the claim limitations recited in instant claim 17, wherein controlling parasitic mites and/or ticks in a bee colony would be achieved by delivering a bee-safe acaricide to the bee colony.
From the teachings of the references, the Examiner recognizes that 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 modify Storm’s method of delivering a biologically active chemical agent to an arthropod pest of a bee by substituting the biologically active chemical agent (i.e., carnauba wax particles, oil of rosemary, cedarwood oil, camphor oil, chamomile oil, menthol or thymol or a combination of thymol and at least one other oil) with one or more peptide analogs or peptidomimetics of proctolin (i.e., peptide analogs or peptidomimetics with substitutions at the second and fourth position as in R[Phe(4-F)]L[HyP]T; or with substitutions at its fourth position as in RYL[HyP]T) as the acaricide (miticide) against tracheal mites and/or varroa mites that affect commercial and domestic strains of Apis mellifera species.
One of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to do so because: proctolin analogs have been evaluated for its insecticidal activity, because as taught by Konopinska: structural modifications of proctolin include a consecutive replacement of native amino acid residues at any of the five positions of the peptide chain by other natural or non-natural amino acids, modifications at position Tyr2 for [Phe(p-F)2] are important in preserving full proctolin myostimulatory properties and agonistic activity in relationship to the RYLPT proctolin; and because as taught by Konopinska: the presence of pyrrolidine substituted system with 4’ – OH as the fourth residue in the pentapeptide (i.e., Arg-Tyr-Leu-Hyp-Thr) is a more cardioactive agonist than the pentapeptide comprising homo-Pro.
Furthermore, one of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to make the substitutions because the proctolin and/or proctolin receptor gene has not been identified in genomes of A. mellifera, where proctolin and its receptor are now considered absent as taught by Caers. Therefore, controlling parasitic mites and/or ticks in a bee colony by delivering an acaricide comprising a peptide analog or peptidomimetic of proctolin would be a bee-safe method of controlling the parasites in the bee colony.
One of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated with reasonable expectation of success to make the substitutions given that the biologically chemical agent (i.e., carnauba wax particles, oil of rosemary, cedarwood oil, camphor oil, chamomile oil, menthol or thymol or a combination of thymol and at least one other oil) of Storm was provided in order to control parasitic mites and/or ticks in a bee colony. Given that the proctolin analogs of Konopinska modified at position 4 have an agonistic effect on the heat-beat frequence of insects. Given that proctolin is not restricted to the cockroach nor to insects and proctolin itself or closely related peptides exist outside the arthropods as taught by O’Shea. Therefore, substituting the biologically chemical agent of Storm with a proctolin analog such as Ac-R[Phe(4-F)]L[HyP]T or RYL[HyP]T, in a method of delivering a biologically active chemical agent to an arthropod pest of a bee colony would support the instantly claimed method of controlling parasitic mites and/or ticks, in a bee colony comprising delivering a bee-safe acaricide to the bee colony by constituting a simple substitution of one known element for another to obtain predictable results and/or some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention pursuant to KSR.
Regarding claims 18, 21-22 and 24, wherein said delivering comprises placing said acaricide inside a bee colony enclosure, or outside the bee colony enclosures proximate to the enclosure where bees will otherwise come into contact with said acaracide, as recited in instant claim 18; wherein said bee colony enclosure is a hive or brood box, as recited in instant claim 21; wherein said bee-safe acaracide delivered as a bee-safe acaracide composition comprising said bee-safe acaracide dispersed in a dry or liquid carrier, as recited in instant claim 22; wherein said bee-safe acaracide is dispersed in a dry carrier, wherein said delivering step comprises dusting said bee colony with said bee-safe acaracide composition, as recited in instant claim 24; and wherein said bee-safe acaracide composition is selected from the group consisting of powders, granules, flakes, crumbles, compressed tablets, patties, and cakes, as recited in instant claim 26.
Storm teaches that since the bee is the carrier of the biologically active chemical, the behavior of the bee can be utilized to deliver the biologically active agent(s) to the target organism or environs thereof (see pg. 2, para[0020]). For example, the natural grooming action of bees will also tend to help with the dispersal of particles of the invention in the hive and with the removal of mites from the bee (see pg. 2, para[0020]). Storm also teaches that the target site of the biologically active chemical may be a target organism (i.e., varroa mite) or it may be a discrete location such as a honeycomb in which the organism is found (see pg. 2, para[0018]). Storm adds that the term “discreate location” refers to a location wherein the target organism lives, feeds, inhabits or wherein it can be found; this might include for example a honeycomb, a nest , a plant, a hive, structural timbers of a mound (see pg. 2, para[0021]). Storm adds that the carnauba was in electrostatic powder form, was sprinkled directly over the top of the brood frames (see pg. 4, para[0050]). Since Storm teaches that biologically chemical agent (i.e., the carnauba wax) was in electrostatic powder form, and since the natural grooming action of bees will also tend to help with the dispersal of particles, it must follow that Storm’s biologically chemical agent is dispersed in a dry carrier; is dusted in the bee colony and it consists of a powder. As such, the teachings of Storm are suggestive of the claim limitations recited in instant claims 18 , 21-22, 24 and 26.
Regarding claims 23 and 25, Storm does not expressly teach wherein said bee-safe acaracide is dispersed in a liquid carrier, wherein said delivering step comprises spraying said bee-safe acaracide composition on said bee colony or feeding said bee-safe acaracide composition to bees of said colony, as recited in instant claim 23; nor wherein said bee-safe acaracide composition is edible by bees or bee larvae, as recited in instant claim 25.
However, Schmid teaches a process for controlling parasitic honeybee mites, such as Varroa jacobsoni, Acarapis woodi and Tropilaelaps clareae and compositions for controlling honeybee mites, where the active ingredients are administered in physiologically compatible preparations to the bees as feed or are applied in the beehive (see abstract). Schmid claims that the process for controlling mites parasitizing on honeybees is effected by fumigating, spraying, atomizing, dropping or feeding the active ingredients/compounds to or on the bees (see column 10, claim 2). Schmid adds that the compounds exhibit a systemic action that renders possible their administration by way of the organs of the bee which effect the absorption of food and liquid, so that in this manner the said compounds, acting through the haemolymph of the bee, have a direct toxic effect on the sucking mites present (see column 2, lines 21-27). Schmid also claims that the administering is effected by feeding said compound in a sugar solution to the bees (see column 10, claims 3-4, lines 37-42). As such, the teachings of Storm when combined with the teachings of Schmid are suggestive of the claim limitations recited in instant claims 25 and 25.
From the teachings of the references, the Examiner recognizes that 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 modify Storm’s method of delivering a biologically active chemical agent to an arthropod pest of a bee by incorporating the teachings of Schmid and controlling parasitic honeybee mites by feeding a compound in a sugar solution to the bees; in order to arrive at the claimed method of controlling parasitic mites wherein said bee-safe acaricide is dispersed in a liquid carrier and wherein said bee-safe acaricide composition is edible by bees or bee larvae.
One of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to do so because controlling honeybee parasites by way of the organs of the bee which effect the absorption of food and liquid, so that in this manner the said compounds (i.e., acaricide), acting through the haemolymph of the bee, have a direct toxic effect on the sucking mites present as taught by Schmid. One of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated with reasonable expectation of success to fumigate, spray, atomize, drop or feed the active ingredients/compounds (i.e., acaricide) to or on the bees given that these administration techniques were known to control mites parasitizing on honeybees. Therefore, incorporating Schmid’s teachings as part of a method of delivering a biologically active chemical agent to an arthropod pest of a bee colony would support the instantly claimed method of controlling parasitic mites and/or ticks, in a bee colony comprising delivering a bee-safe acaricide to the bee colony by constituting some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention pursuant to KSR.
From the teachings of the references, it is apparent that 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 was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Response to Arguments
Applicants arguments filed 03/26/2026, with respect to the 35 U.S.C 103 rejection of claims 17-18 and 21-26, have been fully considered but they are not persuasive for the following reasons:
In response to Applicants’ argument, i.e., the combination of references fails to provide an articulated reasoning with a rational underpinning and does not supply a reasonable expectation of success to arrive at the claimed method using the specifically recited proctolin-derived peptide analogs/peptidomimetics in a bee colony as the bee-safe acaricide, nor does it explain how the proposed combination yield a predictable result (see Remarks, filed 03/06/2026, pg. 5, third paragraph); have been fully considered, but are not persuasive.
Pursuant to MPEP 2143.02(II), obviousness does not require absolute predictability, however, at least some degree of predictability is required. Evidence showing there was no reasonable expectation of success may support a conclusion of nonobviousness. In re Rinehart, 531 F.2d 1048, 189 USPQ 143 (CCPA 1976). As previously discussed, the teachings of Storm, Konopinska, Konopinska 2, Caers , Schmid and O’Shea are suggestive of the claim limitations as recited in instant claims 17-18, and 21-26.
Storm expressly teaches a method of controlling an arthropod pest of a bee by administering a biologically active chemical agent that has a population controlling action against tracheal mites and/or varroa mites that affect commercial and domestic strains of Apis mellifera species. Thereby, an ordinary skilled artisan would have been motivated to control an arthropod pest in a bee colony after reading Storm.
Konopinska and Konopinska 2, expressly teach analogues of proctolin that comprise substitutions at positions 2 and 4 of the pentapeptide YRLPT. The Konopinska references teach the effects of modifying each position of the pentapeptide in relation to the pentapeptide myotropic effect and agonistic influence on the heart-beat frequency of insects. Thereby, an ordinary skilled artisan, after reading the Konopinska references would have been motivated to use proctolin analogues as part of a method to control an arthropod pest in a bee colony.
Caers teaches RYLPT is a myo- and neurostimulatory neuropeptide of which the appearance seems to be restricted to arthropods and that proctolin receptor and that no proctolin gene has been identified in genomes of A. mellifera (i.e., common name Western Honey bee or European Honey bee), where proctolin and its receptor are now considered absent. Thereby, an ordinary skilled artisan would have been motivated with reasonable expectation of success to use proctolin in a bee colony, without negatively affecting the bees.
Schmid teaches a process for controlling parasitic honeybee mites, such as Varroa jacobsoni, Acarapis woodi and Tropilaelaps clareae and compositions for controlling honeybee mites, where the active ingredients are administered in physiologically compatible preparations to the bees as feed or are applied in the beehive. Schmid adds that liquid administration of a compound through the haemolymph of the bee, have a direct toxic effect on the sucking mites present. Thereby, an ordinary skilled artisan after reading Schmid would have been motivated to deliver the proctolin analog in liquid form.
O’Shea teaches that proctolin is not restricted to the cockroach nor to insects and that proctolin itself or closely related peptides exist outside the arthropods. O’Shea adds that once synthetic proctolin became available it was possible to examine its bioactivities in a variety of preparations which include contraction of insect skeletal muscle, myogenic rhythm of contraction and relaxation, long-lasting contracture without depolarizing the muscle, involvement as a co-transmitter in the process of skeletal neuromuscular transmission, and effects on the CNS of insects as well as the effects on the insects heart. Thereby, an ordinary skilled artisan after reading O’Shea, would have been motivated with reasonable expectation of success to use proctolin analogs in order cause long-lasting contracture without depolarizing of the parasitic mites’ and/or ticks’ muscles; as part of a method of controlling parasitic mites and/or ticks in a bee colony without negatively affecting the bees.
Therefore, the applied art shows ample suggestion that substituting Storm’s biologically active chemical agent with one or more proctolin analogs or peptidomimetics would result in the claimed method of controlling parasitic mites and/or ticks in a bee colony. Absolute predictability is not a necessary prerequisite to a case of obviousness. Rather, the applied art conveys a degree of predictability that one of ordinary skill in the art would have found to be reasonable sufficient.
Additionally, pursuant to MPEP 2145 (IV), one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In the instant case Applicants’ reply is directed to what the applied references fails to teach and also fails to address the combined teachings of the applied references; thus Applicants’ arguments attack each reference individually.
Applicants are respectfully reminded the test for obviousness is what the combined teachings of the references would have suggested, instead of what each individual reference teaches. Therefore, an ordinary skilled artisan after reading the teachings of the applied art would have been motivated with reasonable expectation of success to arrive at the claimed method. The 35 U.S.C 103 rejection above is based on the teachings of six different references, which when combined provide motivation (as discussed above) to arrive at the instantly claimed method.
Additionally, pursuant to MPEP 2142, 35 U.S.C 103 authorizes a rejection where, to meet the claim, it is necessary to modify a single reference or to combine it with one or more other references (emphasis added). Since the rejection is based on obviousness, it is unnecessary for every claim limitation to be taught and/or suggested by a single reference. Additionally, obviousness may 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), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007).
As such, the question is (1) whether a person of ordinary skill in the art would be motivated and/or expected that a proctolin peptide analog or peptidomimetic comprising substitutions at positions 2 and 4 of the pentapeptide, where the substitutions comprise Phe(4-F) and/or Hyp would be an effective method of controlling parasitic mites and/or ticks in a bee colony; and (2) whether a person of ordinary skill in the art would be motivated and/or expected to administer a bee-safe acaricide comprising a peptide analog or peptidomimetic via a liquid carrier so that the acaricide affects the parasites through the haemolymph of the bee. The Examiner maintains that the answers to these questions are yes in light of the teachings of Storm, Konopinska, Konopinska 2, O’Shea and Caers for question one and Storm, O’Shea and Schmid for question two.
In response to Applicants’ arguments, i.e., the applied combination of art fails to supply a reasoned motivation with rational underpinning and a reasonable expectation of success to arrive at the claimed invention without hindsight (see Remarks, filed 03/06/2026, pg. 5, third paragraph); it is found unpersuasive.
It must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Additionally, it is the Examiner’s understanding that Applicants are suggesting that the Examiner’s position fails to establish a prima facie case of obviousness because the prior art does not lead an artisan to the instant invention. If Applicants mean to suggest that the Examiner arrived at the instantly claimed invention via the use of improper hindsight, this is not persuasive because any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the Applicants disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). Here, Applicants fail to identify a single aspect of the claimed invention that was not taught, disclosed, or suggested by the prior art relied upon by the Examiner.
Accordingly, the 35 U.S.C 103 rejection to claims 17-18 and 21-26, has been maintained.
Conclusion
No claims are allowed.
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/CLAUDIA ESPINOSA/Patent Examiner, Art Unit 1654
/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654