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 .
Priority
This application claims the benefit of and priority of PCT/US2022/076440 filed 09/14/2022, which claims benefit of 63/244,353 filed on 09/15/2021, 63/344,440 filed on 05/20/2022, and 63/400,014 filed on 08/22/2022 is acknowledged.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 07/15/2024 and 11/24/2025 was filed prior to the mailing of the instant first Office action on the merits. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Rejections - 35 USC § 102
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.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-3, 14, 21, 25, 72, 75 and 77 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Mandinova et al (WO 2013/163512 A1).
Regarding claim 1, the method of treating a cutaneous lesion topically with a compound comprising:
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is anticipated by Mandinova et al, referenced as the compound A-443654 26 (pg. 34, ¶107) as a known ATK inhibitor within the reference. Additionally, the reference art claims (reference claims 1 and 2), where “…the method comprising administering a therapeutically effective amount of a composition that inhibits the Akt signaling pathway to a subject having a seborrheic keratosis.”, and where the composition is applied topically or systemically.
Regarding claims 2-3 and 14, Mandinova et al, anticipates the cutaneous lesions as keratosis and where the keratosis is seborrheic keratosis (SK). Mandinova notes throughout the reference that these lesions (as a general description) develop commonly in the human population (often age related) and from malignant and benign cancer cells. It is further described where these lesions, while benign often develop in to seborrheic keratosis (¶003).
Regarding claim 21, Mandinova et al anticipates the treatment inducing apoptosis of a keratinocyte in the cutaneous lesion. Mandinova et al discloses in Example 2: Primary SK cells are dependent on activated Akt signaling for survival (¶106-107), where the experiments were performed from a collection of small molecule kinase inhibitors to determine which inhibitors were effective and by specific targeted pathways with results in Fig4 and Fig 4A.
Regarding claims 72, 75 and 77, Mandinova et al, anticipates the compound of the instant claim 1, a method of treating a skin disease, comprising administering to the subject a topical composition (instant claims 72 and 75) and where the condition is seborrheic keratosis (instant claim 77). As described in “Detailed Description of the Invention”, Mandinova et al discloses (¶044) “Provided herein are methods and assays for isolating and culturing seborrheic keratosis cells ex vivo, a technique that permits study of these cells in culture. Also provided herein are screening assays using cultured seborrheic keratosis cells and methods for treating seborrheic keratosis in a subject.”. Mandinova et al also notes (p22, ¶086), where “Essentially any small molecule inhibitor of the Akt signaling pathway can be used in the treatment of seborrheic keratosis using methods described herein.”. Furthermore, Mandinova et al claims (reference claims 1 and 2, .pdf p.40) “A method for treating a seborrheic keratosis in a subject, the method comprising administering a therapeutically effective amount of a composition that inhibits the Akt signaling pathway to a subject having a seborrheic keratosis.”, and “…wherein the composition is applied topically or administered systemically.” (reference claim 2).
Claim Rejections - 35 USC § 103
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.
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.
Claim(s) 4-5, and 7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mandinova et al (WO 2013/163512 A1).
Mandinova et al teaches the following in reference to the composition and administration of the compound of claim 1:
The dose of the reference compound of instant claim 1 (aka A-443654 in the reference art), can be administered daily from weeks to months (¶091, Pharmaceutically acceptable carriers);
The route of administration at a desired site, the mode of administration includes: injection, infusion, instillation, topical or ingestion to a human subject (¶089-090, Dosage, administration and efficacy);
Where the composition is a topical composition (as in claim 72). As disclosed in Example 2, (p34, ¶110) “SK explants were treated by topical application…”;
Mandinova et al does not teach the following:
Where the composition is administered from one to four times daily (claim 4);
Where the compound is administered for about 14-28 days (claim 5)
Where the composition is administered in a cycle of twice daily for 4 days, and no administration for about four days (claim 7);
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing dated of the claimed invention, to arrive at the instantly claimed invention where the subject would have administered the compound of the instant claim 1, topically for the durations as claimed for the following reasons:
Regarding claims 4-5, and 7 where Mandinova et al does not specifically identify the duration, intervals or the specific composition in gel form for the compound of instant claim 1 to be administered, it would have been reasonable to conclude that one skilled in the art would have administered the compound for the duration and intervals in a gel composition of the instant claim because as disclosed by Mandinova, “…can be ascertained by routine methods such as modeling, dose escalation studies or clinical trials, and by taking into consideration routine factors, e.g., the mode or route of administration of agent delivery, the pharmacokinetics of the composition, the severity and course of the disorder or condition, the subject’s previous or ongoing therapy, the subject’s health status and response to drugs, and the judgement of the treating physician.” (p25, ¶090). Therefore, per MPEP 2144.05 it would have been routine optimization to arrive at the claimed invention and why a person of ordinary skill in the art would have had a reasonable expectation of success to formulate the claimed duration of treatment, intervals of treatment and gel formulation for the administration and composition of the compound of the instant claims to decrease the symptoms, number, size and/or severity of cutaneous lesions and/or seborrheic keratosis.
Claim(s) 23, 25-26, 39-40, 55, 57, and 72 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mandinova et al (WO 2013/163512 A1) and further in view of Jantharaprapap et al. ("Effects of penetration enhancers on in vitro permeability of meloxicam gels"; Inter J of Pharceutics; 10/2007; vol 343 (issue 1-2), 26:33).
Mandinova et al teaches the following in reference to the composition and administration of the compound of claim 1:
The route of administration at a desired site, the mode of administration includes: injection, infusion, instillation, topical or ingestion and a human subject (¶089-090, Dosage, administration and efficacy);
Where the composition is a topical composition (as in claim 72). As disclosed in Example 2, (p34, ¶110) “SK explants were treated by topical application…”;
Mandinova et al does not teach the following:
Where the composition is a gel formulation (claim 23 and 26);
Where the composition propylene glycol is present in the amount of 10-20% (claims 25, 39 and 57);
Where the composition is 2-(2-ethoxyethoxyl)ethanol is present in the amount of 40-60% (claims 25, 40, and 57);
Where hydroxypropyl cellulose is .5-5% (claims 25, 55, and 57), propylene glycol is 10-20% (claims 25 and 57).
Jantharaprapap et al. teaches the gel formulation as in the instant claims, where the compounds comprise (2.3.1 Gel Formulations/Selection of co-solvents, p27) of propylene glycol 10-20%, 2-(2-ethoxyethoxyl)ethanol 40-60%, Hydropropyl cellulose .5-5% and propylene glycol is 10-20%. Jantharaprapap et al. includes the gel formulation as multiple formulations (see Table 1: F#1, p27).
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Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing dated of the claimed invention, to arrive at the instantly claimed invention where the gel formulation would be comprised as in the instant claims for the following reasons:
Regarding claims 23, 25-26, 39-40, 55, 57, and 72 and the components of the gel formulation which comprises propylene glycol 10-20%, 2-2(2-ethoxyethoxy)ethanol 40-60%, and hydroxypropyl cellulose 0.5-5% concentrations as listed in the instant claims. It would be reasonable to conclude that one skilled in the art would use a similar, or same, or modify the concentrations of the formulation for the treatment of seborrheic keratosis because the excipient combination represents a well-known and routinely employed gel formulation platform to deliver topical and/or transdermal delivery. Additionally, similar formulations. Therefore, per MPEP 2144.05 it would have been routine optimization to arrive at the claimed invention and why a person of ordinary skill in the art would have had a reasonable expectation of success to formulate the claimed gel formulation by using or modifying the excipient concentrations to deliver the Akt inhibitor compound topically.
Claim(s) 13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mandinova et al (WO 2013/163512 A1) and further in view of Tan et al. (“The Benefits of Occlusive Dressings in Wound Healing”, Open Dermatol Journal, 2019; DOI:10.2174/1874372201913010027.
Mandinova et al. teaches a method for the treating of seborrheic keratosis where an effective amount of an Akt inhibitor is administered topically. However, Mandinova et al. does not teach where the application comprises occlusion of the cutaneous lesion.
Tan et al. teaches generally the benefits of occlusive dressings in wound care management, and that dressing selection is based on needs and/or reasons to use a dressing. Tan further discloses where occlusive dressings increase the process of re-epithelialization or healing processes (Section 3, ¶3), and where fluid in the wound improves healing due to the interaction of regeneration of epithelium, dermal and granulation tissue (Section 3, ¶6). Additionally, Tan et al. discloses (Section 5) the different types of occlusive dressings to include: polymer films, polymer foams, hydrogel dressings, hydrocolloid dressings and alginates. It is further disclosed an indication for occlusive dressings would include wound treatment which can be combined with antibiotics, sponge, hydrogels or any other method for treatment, and where pressure to the ointments improve absorption into the wound and prevents evaporation.
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing dated of the claimed invention, to arrive at the instantly claimed invention where the treatment further comprises occlusion of the cutaneous lesion would be used for the treatment of seborrheic keratosis for the following reasons:
Regarding claim 13, Mandinova et al. does not specifically state that an occlusive dressing was used to topically administer the Atk inhibitor to subject needing treatment as claimed, it would be reasonable to conclude that one skilled in the art would apply an occlusive dressing to someone needing treatment for seborrheic keratosis because as previously stated, it would be indicated to apply an occlusive dressing to promote healing, maintain moisture, to use in combination with other treatments, and to apply pressure to improve absorption of compounds into the wound.
Claim(s) 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mandinova et al (WO 2013/163512 A1) and further in view ofPascoe et al. (“Using the Physician Global Assessment in a Clinical Setting to Measure and Track Patient Outcomes”, JAMA Dermatol, 2015; 151(4):35-381, DOI:10.1001/jamadermatol.2014.3513.
Mandinova et al teaches (¶058-061, Diagnosing Seborrheic Keratosis) the characterized appearance of SKs with descriptors to include the color and size (¶059). Mandinova et al further discloses that “Seborrheic keratosis can be easily diagnosed visually by one of skill in the art of medicine, particularly dermatology.” (¶061) with further elaboration into the color, location and general appearances. Mandinova et al does not teach where the diagnosis is the result of a “named” standardized test or evaluation method such as the Physician’s Lesion Assessment (PLA) in the instant claims or where treatment comprises an improvement of one or more grades in PLA.
The reference Pascoe et al teaches the Physician Global Assessment (PGA), as a tool that scores and tracks a patient’s condition over time. The basis for the study was conducted using a 5- or 6- point scoring system to determine severity (p. 376, col 1, ¶2) to evaluate psoriasis, and where the FDA currently recommends that PGAs be used to evaluate the treatment success for acne vulgaris with a score of clear to almost clear or a 2-point scale reduction for a successful treatment response (p.276, col 1, ¶4). As established in Table 1, which establishes the grading scale for severity, and as noted in the study, PGAs can be used to measure the effects of implementation or guidelines or other care interventions on outcomes. Finally, PGAs provide a quantifiable metric to demonstrate improvements under dermatologic care (p380, col 1, ¶1).
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Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing dated of the claimed invention, to arrive at the instantly claimed invention where the treating comprises the improvement of one or more grades in PLA for the following reasons::
Regarding claim 16, where Mandinova et al, does not specifically state where the treatment for seborrheic keratosis was the result of an improvement in Physician’s Lesion Assessment (PLA) as named (instant claim 16), it would be reasonable to conclude that one skilled in the art would conduct a physical examination and establish treatments based on the criteria of standardized practice of observations of any and/or all skin changes because the observed skin changes which include the size, location, color and textures are part of the standard examination processes for the diagnosis of SKs. Additionally, it would also be reasonable to conclude that one skilled in the art would use a tool such as a Physician Global Assessment (aka Physician Lesion Assessment), to determine if was an improvement by one or more categories because the PGA/PLA is standardized to collect and monitor severity over time, is customizable based on the conditions being monitored and will allow physicians to determine the effectiveness of treatment or if changes in treatment regime are needed.
Summary of the Claims
Claims 1-5, 7, 13-14, 16, 21, 23, 25-26, 39-40, 55, 57, 72, 75 and 77 are pending.
Claims 1-5, 7, 13-14, 16, 21, 23, 25-26, 39-40, 55, 57, 72, 75 and 77 are rejected.
Conclusion
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/S.H.D./Examiner, Art Unit 1627
/Kortney L. Klinkel/Supervisory Patent Examiner, Art Unit 1627
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