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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 February 20, 2026 has been entered.
Detailed Action
This office action is a response to applicant’s communication submitted February 20, 2026 wherein claims 18 and 28 are amended. This application claims benefit of provisional applications 63/199447, filed December 29, 2020, and 63/199422, filed December 24, 2020.
Claims 18, 23, 24, 26, 28, and 29 are pending in this application.
Claims 18, 23, 24, 26, 28, and 29 as amended are examined on the merits herein.
Withdrawn Rejections
Applicant’s amendment, submitted February 20, 2026, with respect to the rejection of claims 18, 23, 24, 26, 28, and 29 under 35 USC 112(b) for containing contradictory limitations as to whether or not the composition can contain further ingredients, has been fully considered and found to be persuasive to remove the rejection as the claims have been amended so as to make it clear that the phrase “consisting of” applies only to the active ingredients. Therefor ethe rejection is withdrawn.
The following rejections of record in the previous action are maintained:
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.
Claims 18, 23, 24, 26, and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Kaoukhov et al. (US 20080194664, of record in previous action) in view of Tamarkin et al. (US 20180064638, of record in previous action) in view of Lipozencic et al. (Clinics in Dermatology (2011) 29, 157-161, of record in previous action) in view of Tempark et al. (Reference of record in previous action) in view of Barańska-Rybak et al. (“New indications for topical ivermectin 1% cream: a case series study,” Adv Dermatol Allergol 2019; XXXVI (1): 58–62, Reference of record in previous action)
Claim 18 is drawn to a method for treating a patient suffering from perioral dermatitis comprising administering to the patient a formulation comprising: a) an avermectin compound or a pharmaceutically acceptable salt thereof; b) a nitroimidazole compound or a pharmaceutically acceptable salt thereof, and c) a macrolide antibiotics compound or a pharmaceutically acceptable salt thereof, and a dermatologically acceptable carrier, at various broadly defined concentrations. Dependent claims 23, 24, and 27 further specify the concentrations of the different active agents. Dependent claims 26 and 28 specify additional active ingredients to be included in the composition.
Kaoukhov et al. disclose pharmaceutical/dermatological compositions containing at least one avermectin compound, e.g., ivermectin and metronidazole (a nitroimidazole compound) or salt, ester or derivative thereof, that are useful for treating afflictions of the skin, especially rosacea (see abstract). Furthermore, Kaoukhov et al. disclose that conventionally, rosacea is treated orally or topically with antibiotics such as tetracyclines, erythromycin or clindamycin, but also with vitamin A, salicylic acid, anti-fungal agents, steroids, anti-infectious agents such as benzoyl peroxide, or with isotretinoin in severe cases or even with metronidazole (an anti-bacterial agent) (see page 1, [0015]). Also, Kaoukhov et al. disclose that the compositions according their invention are pharmaceutical compositions, and especially dermatological compositions, which may be in any galenical form conventionally used for topical application and especially in the form of creams, aqueous gels, and aqueous or aqueous-alcoholic solutions (see pages 2-3, [0045]). Furthermore, Kaoukhov et al. disclose that propylene glycol can be used in their composition (see page 3, [0049]). Also, Kaoukhov et al. disclose that fatty alcohols such as cetyl alcohol, fatty acids, waxes and gums, in particular silicone gums, may also be used as fatty substances in their composition (see page 3, [0047]). In addition, Kaoukhov et al. disclose that in the compositions according to their invention, the said compound of the avermectin family is present in concentrations of from 0.001 % to 10% by weight and preferably from 0.01 % to 5% by weight relative to the total weight of the composition (see page 2, [0033]). Also, Kaoukhov et al. disclose that according to a first embodiment of their invention, the subject compositions are useful for formulating medicaments for treating the skin and preferably for treating rosacea, common acne and seborrheic dermatitis and particularly preferably for treating rosacea (see page 2, [0043]). The difference between Applicant's composition and the composition taught by Kaoukhov et al. is that Kaoukhov et al. do not explicitly disclose that their composition comprises dermatologically acceptable carrier and macrolide antibiotics compound.
Tamarkin et al. disclose compositions and methods for treating rosacea and acne (see abstract). Furthermore Tamarkin et al. disclose that specifically, a gel or foam composition having a tetracycline antibiotic and uses thereof for treating rosacea and acne are provided (see abstract). Also, Tamarkin et al. disclose that their method includes administering topically to a surface having the disorder a therapeutic hydrophobic composition comprising a tetracycline antibiotic. In one or more embodiments, the hydrophobic composition comprises a carrier comprising about 60% to about 99% by weight of at least one hydrophobic solvent; at least one viscosity-modifying agent selected from the group consisting of a fatty alcohol, a fatty acid and a wax; and a tetracycline antibiotic (see page 3, [0040]). In addition, Tamarkin et al. disclose that surfactants can be used in their composition (see page 5, [0065] - [0067]); see also page 6, [0077] - [0078]).
It would have been obvious to one having ordinary skill in the art, at the time of the effective filing date, in view of Kaoukhov et al. and Tamarkin et al. to prepare a formulation or composition to treat rosacea that comprises an avermectin compound such as ivermectin and a nitroimidazole compound such as metronidazole as taught by Kaoukhov et al., and to include in the composition a macrolide antibiotics compound such as the tetracycline, erythromycin as suggested by Kaoukhov et al., and fatty acid or wax (a dermatologically acceptable carrier) as taught by Kaoukhov et al. and Tamarkin et al., and which have the same utility of treating skin conditions and afflictions, and especially for treating rosacea, based on factors such as the severity of the rosacea or treating skin condition.
One having ordinary skill in the art would have been motivated, in view of Kaoukhov et al. and Tamarkin et al. to prepare a formulation or composition to treat rosacea that comprises an avermectin compound such as ivermectin and a nitroimidazole compound such as metronidazole as taught by Kaoukhov et al., and to include in the composition a macrolide antibiotics compound such as the tetracycline, erythromycin as suggested by Kaoukhov et al., and fatty acid or wax (a dermatologically acceptable carrier) as taught by Kaoukhov et al. and Tamarkin et al., and which have the same utility of treating skin conditions and afflictions, and especially for treating rosacea, based on factors such as the severity of the rosacea or treating skin condition.
It is obvious to use a carrier that comprises a surfactant such as the non-ionic surfactant, PEG 150 distearate (which has good thickening efficiency), especially since Tamarkin et al. disclose that the surfactant PEG 150 distearate can be used in their composition (see page 53, [0578]). Also, it is obvious to use a hydrophobic solvent in percent by weight such as 50% as taught or suggested Tamarkin et al. (see page 10, [0120]), and to also use the fatty acid or wax (i.e.; a dermatologically acceptable carrier) in % by weight such as 10% as taught by Tamarkin et al. (see page 10, [0129] - [0132]). It should be noted that 10% by weight of the dermatologically acceptable carrier (fatty acid or wax) and 50% by weight of solvent equates to the carrier comprising 20% by weight of the solvent (i.e.; (10/50) x 100). In addition, it is obvious to use the solvent, PPG-15 stearyl ether disclosed by Tamarkin et al. (see page 9, [0117]). Also, it is obvious to use an addition tetracycline based on factors such as the severity of the treating skin conditions or rosacea, and especially since Kaoukhov et al. and Tamarkin et al. disclose or suggest that antibiotics can be used.
Regarding the amended concentration values present in claim 18, and the narrower concentrations recited in dependent claims 23 and 24, Kaoukhov et al. discloses preferred concentration ranges of 0.01-5% for the avermectin compound and 0.1-2% for metronidazole. (p. 2 paragraphs 33-34) Tempark et al. discloses a review of various treatments for perioral dermatitis including topical metronidazole at 1%-2%, (p. 109 section 6.6) and topical erythromycin at 1 or 1.5%. (p. 109 section 6.7) While oral antibiotics were found to be more effective than topical treatment, topical treatment was suggested as a first-line treatment because it has no gastrointestinal side effects. It would have been obvious to one of ordinary skill in the art at the time of the invention to determine the appropriate concentration for each of these active ingredients in a combined formulation, using the concentrations suggested in the art a s a starting point.
Furthermore Kaoukhov et al. and Tamarkin et al. do not disclose using their formulation to treat perioral dermatitis. However, Lipozencic et al. disclose that perioral dermatitis is a relatively common inflammatory disorder of facial skin, often appearing in patients with rosacea, but with less inflammation (see abstract). Furthermore, Lipozencic et al. disclose that treatment of perioral dermatitis may include topical metronidazole as for rosacea (once or twice daily), topical erythromycin, clindamycin, or tetracycline (see abstract).
Additionally, Barańska-Rybak et al. discloses a case series study of a population of patients suffering from inflammatory dermatoses treated with topical 1% ivermectin. (p. 59 “Materials and Methods”) Complete or almost complete clearance was observed in all eight patients suffering from perioral dermatitis. (p. 59 right column second paragraph)
It would have been obvious to one having ordinary skill in the art to treat peri-oral dermatitis in a patient comprising administering the formulation or composition taught or suggested by Kaoukhov et al. and Tamarkin et al. to said patient, especially since Kaoukhov et al. and Tamarkin et al. disclose or suggest that the said composition can treat dermatitis, and Lipozencic et al. and Barańska-Rybak et al. disclose that these same agents can treat peri-oral dermatitis, thereby suggesting their combination.
For these reasons the invention taken as a whole is prima facie obvious.
Claim 29 is rejected under 35 U.S.C. 103(a) as being unpatentable over Kaoukhov et al. in view of Tamarkin et al. in view of Lipozencic et al. in view of Tempark et al. Barańska-Rybak et al. as applied in claim 18 above, and further in view of Alam et al. (Iranian Journal of Pharmaceutical Research (2016), 15 (1): 35-52, of record in previous action).
The difference between Applicant’s composition and the method taught by the cited prior art references is that the prior art does not disclose the hydrophilic/lipophilic balance (HLB) of the composition.
Alam et al. disclose studies involving the anti-dermatitis potential of nanoemulsion formulation for topical delivery (see abstract and Title). Furthermore, Alam et al. disclose an aspect to be taken into consideration is the selection of surfactants; ideally the hydrophilic lipophilic balance (HLB) value to form the o/w nanoemulsion should be greater than 10. The right blend of low and high HLB surfactants leads to the formation of a stable nanoemulsion formulation
It would have been obvious to one having ordinary skill in the art, at the time of the effective filing date, in view of Kaoukhov et al., Tamarkin et al. and Alam et al. to prepare a formulation or composition such as a stable o/w nanoemulsion with an HLB of greater than 10 such as by using a surfactant with a HLB value of greater than 10 as taught or suggested by Alam et al. to treat perioral dermatitis that comprises an avermectin compound such as ivermectin and a nitroimidazole compound such as metronidazole as taught by Kaoukhov et al., and to include in the composition a macrolide antibiotics compound such as the tetracycline, erythromycin as suggested by Kaoukhov et al., and fatty acid or wax (a dermatologically acceptable carrier) as taught by Kaoukhov et al. and Tamarkin et al., and which have the same utility of treating skin conditions and afflictions.
One having ordinary skill in the art would have been motivated, at the time of the effective filing date, in view of Kaoukhov et al., Tamarkin et al. and Alam et al. to prepare a formulation or composition such as a stable o/w nanoemulsion with an HLB of greater than 10 such as by using a surfactant with a HLB value of greater than 10 as taught or suggested by Alam et al. to treat rosacea that comprises an avermectin compound such as ivermectin and a nitroimidazole compound such as metronidazole as taught by Kaoukhov et al., and to include in the composition a macrolide antibiotics compound such as the tetracycline, erythromycin as suggested by Kaoukhov et al., and fatty acid or wax (a dermatologically acceptable carrier) as taught by Kaoukhov et al. and Tamarkin et al., and which have the same utility of treating skin conditions and afflictions.
Response to Arguments
Applicant’s arguments, submitted February 20, 2026, with respect to the above grounds of rejection, have been fully considered and not found to be persuasive to remove the rejection. Applicant argues that the present invention recognizes a need for a broader spectrum topical formulation for treating perioral dermatitis, as a result of this condition having a variety of root causes. In particular, Applicant claims that the motivation for inclusion of erythromycin in a topical treatment for perioral dermatitis is not clear. Applicant further argues that the presently claimed formulation has additional benefits including longer efficacy, increased time before first relapse, quicker relief, improved satisfaction, and better compliance. Finally, Applicant argues that combination therapy counters emerging resistance of demodex mites to ivermectin.
With regard to the first consideration, it is recognized that, as discussed in MPEP 2143(I)(A), it is prima facie obvious to combine prior art elements according to known methods to yield predictable results. Since all of the active agents recited in the claims were in fact known as individually effective it would have been obvious to combine them into a single formulation containing all three active agents. Regarding the second consideration, while Applicant has repeatedly asserted during prosecution that the present method has unexpectedly improved properties compared to therapy with one or two of the active agents, as stated in MPEP 2145(I), “Arguments presented by applicant cannot take the place of evidence in the record.” In the present application no objective evidence has been provided of the asserted benefits of the claimed method that would allow the examiner to make an objective determination as to whether or not they were expected. Therefore the prima facie case of obviousness cannot be overcome by the mere assertion that there exist additional unexpected benefits.
Regarding the third consideration, according to MPEP 2141.02(III), "[A] patentable invention may lie in the discovery of the source of a problem even though the remedy may be obvious once the source of the problem is identified. This is part of the ‘subject matter as a whole’ which should always be considered in determining the obviousness of an invention under 35 U.S.C. § 103." If Applicant has newly discovered the source of a problem, for example the difficulty of treating perioral dermatitis being due to drug resistance among demodex mites, then a solution to said problem using the claimed invention is nonobvious. However, as discussed in MPEP 2141.02(IV), “Applicants who allege the inventor discovered the source of a problem must provide evidence substantiating the allegation, either by way of affidavits or declarations, or by way of a clear and persuasive assertion in the specification.” In the present case, Applicant’s assertion is not backed up by objective evidence, as there is no clear demonstration in the disclosure that this is in fact the case.
For all of these reasons the rejections are deemed proper and maintained.
Conclusion
No claims are allowed in this action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANDREA OLSON whose telephone number is (571)272-9051. The examiner can normally be reached M-F 6am-3:00pm.
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/ANDREA OLSON/ Primary Examiner, Art Unit 1693 3/4/2026