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 .
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Response to Amendment
The amendment filed January 8, 2026 has been entered. Claims 1, 5-12, and 16-20 have been amended, claims 2-4 and 13-15 are cancelled. Applicant’s amendments to the claims and specification have overcome the specification objections, the 112b rejections and 102 rejections previously set forth in the Non-Final Office Action mailed October 8, 2025. Applicants cancellation of claims 2, 4, 13, and 15 have rendered the corresponding rejections/objections moot. As such, these rejections and objections are hereby withdrawn.
Applicant’s arguments filed January 8, 2026 were fully considered but they were not persuasive. Maintained/modified rejections necessitated by Applicant’s amendment are addressed below.
Claims 1, 5-12, and 16-21 are pending in this application.
Priority
This application is a National Phase of PCT Patent Application No. PCT/BR2021/050487 having International filing date of November 8, 2021, which claims the benefit of priority of Brazil Patent Application No. BR102020022824-2 filed on November 9, 2020. Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been received. The Examiner notes that no English translation has been provided.
New Claim Objections
Claim 21 is objected to under 37 CFR 1.75 as being a substantial duplicate of claim 12. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Maintained/Modified 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 1, 5-7, 10-12, 16-18, and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Carreno (WO 2018185685, cited in previous action) as evidenced by Wikipedia (Polysorbate 80, 2025, cited in previous action) in view of Palumbo (American J. Therapeutics, 2009, cited in previous action). The English translation of Carreno has been provided by the Examiner.
Regarding claims 1, 5-7, 10-12, 16-18, and 21: Carreno teaches a topical pharmaceutical composition comprising: at least two pharmaceutical agents selected from the group consisting of pentamidine isethionate, ketoconazole and miltefosine; an agent for boosting skin permeability and a pharmaceutically acceptable vehicle (abstract). The composition is to be used for the treatment of cutaneous leishmaniasis (English translation, pg. 2, field of the invention). Carreno teaches a nanoemulsion cream comprising miltefosine, oleic acid (emollient according to page 16 of the instant specification lines 16-20), water (an excipient), propylene glycol (humectant according to page 16 of the instant specification lines 26-28), and tween 80 (English translation, pgs. 9-10, table 8). Wikipedia discloses Tween 80 (i.e. polysorbate 80) is a nonionic surfactant and emulsifier (pg. 1, top of page, other names). In short, Carreno teaches a topical pharmaceutical composition comprising: a nanoemulsion and at least two pharmaceutical agents selected from the group consisting of pentamidine isethionate, ketoconazole and miltefosine (i.e. antileishmanial agents).
Carreno does not teach wherein the antileishmanial agents are combinations of paromomycin, amphotericin B, meglumine antimoniate as recited by instant claims 4-7 and 15-18.
However, Palumbo teaches that paromomycin, amphotericin B, meglumine antimoniate are known antileishmanial compounds (pg. 180, col. 2, para. 2, pg. 180, col. 1, middle of page, pg. 179, col. 1, para. 1). Wherein Carreno teaches nanoemulsions comprising a combination of antileishmanial compounds, and the art recognizes that paromomycin, amphotericin B, meglumine antimoniate are antileishmanial compounds, it is prima facie obvious to substitute equivalents known for the same purpose (See MPEP 2144.06 (II)).
Taken together it would have been prima facie obvious to modify the composition of Carreno by substituting the antileishmanial agents with paromomycin, amphotericin B, and/or meglumine antimoniate as taught by Palumbo. A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success as the art establishes these compounds are also antileishmanial agents capable of treating the disease, and it is prima facie obvious to substitute equivalents known for the same purpose, absent a showing of unexpected results.
Claims 8-9 and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Carreno (WO 2018185685, cited in previous action), Wikipedia (Polysorbate 80, 2025, cited in previous action), and Palumbo (American J. Therapeutics, 2009, cited in previous action) as applied to claims 1, 5-7, 10-12, 16-18, and 21 above in view of Queiroz (US 9,572,770, cited in previous action).
Regarding claims 8-9 and 19-20: As discussed above, Carreno teaches the composition of claim 1 the method (or use) according to claim 12. Carreno teaches a nanoemulsion cream (i.e. a topical formulation) comprising miltefosine, oleic acid (emollient according to page 16 of the instant specification lines 16-20), water (an excipient), propylene glycol (humectant according to page 16 of the instant specification lines 26-28), and tween 80 (English translation, pgs. 9-10, table 8). Wikipedia discloses Tween 80 (i.e. polysorbate 80) is a nonionic surfactant and emulsifier (pg. 1, top of page, other names).
Carreno does not teach wherein the nanoemulsion comprises an amphoteric surfactant, a moisturizer, and wherein the compound is incorporated into the oil globules of the nanoemulsion in the presence of one or more oxygen carriers as recited by instant claims 8-9 and 19-20.
However, Queiroz teaches an improved nanoemulsion formulation for topical compositions (abstract). Queiroz teaches some advantages of the invention in relation to the active ingredients it aims at dispensing dermally or transdermally include, excellent absorption through the skin, high bioavailability, less administrations per day, absence of first pass metabolism, easy application and higher adhesion of the patient to the therapy (col. 1, lines 55-62). Queiroz teaches the stable topical composition comprises, at least one non-ionic emulsifying agent, at least one amphoteric surfactant, at least one emollient, at least one humectant, and at least a hydrating agent, and one or more active principles (i.e. active compounds or drug) incorporated into the nanoemulsion oleous globules (i.e. oil globules) optionally in the presence of one more oxygen carrying agents (cols. 1-2, bridging para.). Hydrating agents include trehalose, maltose and sucrose (col. 2, lines 32-35). According to the instant specification a moisturizer includes trehalose, maltose, and sucrose (pg. 7, line 3). Thus, the hydrating agents of Queiroz are encompassed by the phrase moisturizer recited by instant claims 8-9 and 19-20. Queiroz teaches there is no specific restriction to the active principles contained in the composition that may be topically applied (col. 2, lines 45-48).
Taken together it would have been prima facie obvious to a person of ordinary skill in the art to modify the nanoemulsion of Carreno by including an amphoteric surfactant, a moisturizer, and wherein the compound is incorporated into the oil globules of the nanoemulsion in the presence of one or more oxygen carriers as taught by Queiroz. A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success as these are known additives to be included in pharmaceutical nanoemulsions for topical administration. It is prima facie obvious to use a known technique to improve similar products (i.e. nanoemulsions) in the same way (See MPEP 2143 (IC)).
Response to Arguments
Applicant’s arguments filed January 8, 2026 with respect the claims have been fully considered but they are not persuasive.
On page 9 of Applicant’s response, Applicant argues that the newly amended claims which specify at least two antileishmanial compounds and further specify further species overcome the 102 rejection over Carreno.
As discussed above, the amendment has overcome the rejection, and this rejection has been withdrawn.
On page 10 of Applicant’s response, Applicant argues that the Examiner suggests it is prima facie obvious to substitute equivalents known for the same purpose, but that an obviousness determination requires articulated reasoning with a rational underpinning, especially when the art teaches away from the claimed invention or presents technical obstacles or unpredictability. On page 11 of Applicant’s response, Applicant argues Carreno is directed to a topical pharmaceutical composition for the treatment of cutaneous leishmaniasis but does not teach the specific combination recited in the amended claims (para. 2). Applicant argues Palumbo teaches away from the present invention and teaches that meglumine antimoniate drug for treating leishmaniasis exists only in parenteral forms and is not ideal due to difficult administration and toxicity, thereby discouraging its use in topical compositions (para. 3). Applicant argues Palumbo further teaches amphotericin B is insufficiently studied with respect to formulation and dosage for cutaneous leishmaniasis (para. 3). On pages 11-12 of Applicant’s response, Applicant summarizes that both Carreno and Palumbo fail to provide any rationale or incentive to combine these agents, especially in light of the known challenges and negative teachings in Palumbo (bridging para.). Applicant states that given the teachings of Palumbo, a person of ordinary skill would lack the motivation to include the specific agents in a stable topical formulation as there is unpredictability in achieving stability, efficacy, and safety for such combinations, particularly when the compounds have differing properties (bridging para.).
However, disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments (See MPEP 2123 (I)). Carreno teaches pentavalent antimonial drugs and amphotericin B are known treatments for leishmaniasis (English translation, pg. 3, para. 2). Palumbo while acknowledging risks and effectiveness associated with topical administration, does not refute its general applicability (pgs. 181-182, bridging para.). An express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982) (See MPEP 2144.06 (II)). Based on the teachings of Carreno and Palumbo, it would be well within the technical grasp to incorporate the claimed antileishmanial ingredients into the antileishmanial formulation of Carreno, and there is requisite motivation to do so given the recognition of these compounds as therapeutically beneficial in treating this disease and there is no explicit teaching away from such an incorporation, only a preference towards other compounds. The art clearly establishes that combination therapies, including topical combination therapies, is a known technique in the art for the treatment of leishmaniasis.
On page 12 of Applicant’s response, Applicant points to Challener, which discusses technical difficulties and unpredictability associated with developing stable and effective topical formulations, especially when multiple active ingredients are involved (para. 2). Applicant also points to Lopez which describes the topical application of amphotericin B was evaluated without significant therapeutic success and thus establishes that simply including an intravenous drug in a topical formulation does not guarantee its therapeutic efficacy in the treatment of leishmaniasis (para. 3).
However, while Challener acknowledges generally that experimentation is required for effective topical formulations, Carreno teaches a viable topical formulation for treatment of leishmaniasis specifically. There is no teaching that additional therapeutic agents, such as those claimed, are incapable of being included in such a formulation. A person of ordinary skill would look to Carreno as a formulation as it includes an agent for boosting skin permeability (abstract). Exchanging active ingredients that are known in the art to be effective in the claimed disease would be within the technical grasp of the skilled artisan. Lopez discloses the efficacy results were not supportive for further clinical development for the treatment of leishmaniasis, however, Lopez also demonstrates that amphotericin is capable of being formulated in a topical formulation and has at the very least, some efficacy, with cure rates of 39% and 35% (pg. 1-2, bridging para.). This ability in the prior art does not teach away from using amphotericin B in a topical formulation, but rather demonstrates its capability to do so, despite efficacy not being where the author wanted it to be.
On pages 13-16 of Applicant’s response, Applicant argues that the 103 rejections over 8-9 and 19-20 should be withdrawn for reasons described above.
See modified 103 rejections and response to arguments above.
Applicant’s reply is considered to be a bona fide attempt at a response and is being accepted as a complete response. The 35 USC § 103 rejection is maintained for reason of record and foregoing discussion.
Conclusion
No claims are allowed in this action.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMUEL L GALSTER whose telephone number is (571)270-0933. The examiner can normally be reached Monday - Friday 8:00 AM - 5:00 PM.
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) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Scarlett Y Goon can be reached at 571-270-5241. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/S.L.G./Examiner, Art Unit 1693
/ANDREA OLSON/Primary Examiner, Art Unit 1693