Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
This office action is in reply to the Applicant’s Election and Remarks filed 04 May 2026 for application 18/411,048 filed 12 January 2024, CIP of PCT/IB22/56437 filed 12 July 2022, CIP of 17/372,649 filed 12 July 2021. Claim 1 is amended. Currently, claims 1-16 are pending.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on 17 January 2024, 10 April 2024, 26 September 2024, 06 February 2025, 17 April 2025, and 24 June 2025 was filed after the mailing date of the application on 12 January 2024. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Election/Restrictions
Applicant’s election of compound IC261, illustrated below, is acknowledged:
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Applicant’s election of sebaceous gland-related disorder is acknowledged.
Applicant's election with traverse of the species election in the reply filed on 04 May 2026 is acknowledged. The traversal is on the ground(s) that 1) the core invention is a unitary biological mechanism, 2) the elected species are exemplary of the mechanism, and 3) search burden is minimized by a mechanism-based strategy. This is found to be persuasive because the independent claim, claim 1, is a method claim in which the elected compound species in dependent claim 2, is utilized.
The species election is withdrawn and all claims will be examined on the merits.
Claim Objections
Claim 1 is objected to because of the following informalities: in the section “A method for reducing size of” should be amended to include the between “reducing” and “size”. Appropriate correction is required.
Claim 9 is objected to because of the following informalities: in the section “wherein the subject suffers from a hair loss.” Should be amended to remove a between “from” and “hair”. Appropriate correction is required.
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.
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 non-obviousness.
Claims 1-7 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over C.C. Zouboulis (1) (Isotretinoin revisited: pluripotent effects on human sebaceous gland cells, J. Investigative Dermatology 2006, 126, 2154-2156), Zhao et al. (Casein kinase 1α interacts with retinoid X receptor and interferes with agonist-induced apoptosis, J. Biol. Chem. 2004, 279, 29, 30844-30849), Nelson et al. (Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action, Dermato-Endocrinology 2009, 1, 3, 177-187) and C. C. Zouboulis (2) (Acne and sebaceous gland function, Clinics in Dermatology 2004, 22, 360-366) in view of Mashhoon et al. (Crystal structure of a conformation-selective casein kinase-1 inhibitor, J. Biol. Chem. 2000, 275, 26, 20052-20060), Ben Neriah et al. (Pyrazole pyrimidine derivative and uses thereof, WO 2017/021969 A1, 2017; entered into the IDS on 10 April 2024).
Zouboulis (1) discloses the antiproliferative effect that isotretinoin has on human sebocytes, attributing a portion of this decrease to cell cycle arrest and detected sebocyte apoptosis (abstract). Retinoids are described to exert their effects by modulating gene expression after binding to and/or activating nuclear retinoid receptors; isotretinoin surprisingly exhibits low binding affinities to both cellular retinoic acid-binding proteins (CRABPs) I and II and nuclear retinoid receptors, retinoic acid receptors (RARs) and retinoid X receptors (RXRs) (pg. 2154 - col. 1). In contrast, stereoisomers tretinoin binds to CRABPs and RARs and ali-tretinoin binds to RXRs as their mechanism-of-action (pg. 2154 – col. 2). Among the various mechanisms, apoptosis has been attributed to RXR nuclear receptor ligands through the reduction of casein kinase 1α (CK1α) by Zhao (pg. 2154 – col. 3).
Zhao discloses a pro-apoptotic pathway that is induced by a RXR agonist is negatively regulated by CK1α. The ability of an RXR agonist to recruit CK1α to a complex with RXR in cells correlates inversely with its ability to inhibit growth, with Zhao showing that CK1α can promote cell survival by interfering with RXR agonist-induced apoptosis (abstract).
Nelson caps this by disclosing insights into the mechanism of action of isotretinoin on acne, a disorder resulting from an over-production of sebum from sebaceous glands resulting in inflammation (Zouboulis (2)), over time, characterizing through pathology, histology and gene expression. Nelson reports significant decreases in sebaceous gland size after 8 weeks of treatment (pg. 178), and of 117 genes that mapped to 10 enriched pathways, 75% of those genes contained RAR or RXR response elements (pg. 181).
They do not, however, teach an inhibitor of CK1α or the CK1 family.
This deficiency is rectified by Mashhoon who teaches the compounds IC261 and CKI7, an ATP competitive inhibitor with activity among CK1 isoforms, including CK1α, CK1δ, and CK1ε. Ben Neriah further teaches compounds A14, A47, A51, A64, and A75 for use in at least one CK1 and IRAK1 inhibition (pg. 22). The compounds read upon formulas II-VI, respectively.
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Ben Neriah further expounds on appropriate pharmaceutical compositions, including topical compositions (pg. 18).
As such, it would have been prima facie obvious, to a person of ordinary skill in the art, before the effective filing date, to consider the use of CK1 inhibitors as taught by Mashhoon and Ben Neriah for the purpose of inhibiting CK1 and more specifically CK1α as Zhao discloses that CK1α negatively regulates a pro-apoptotic pathway of RXR, and Zouboulis (1) discloses that the pro-apoptotic pathway of RXR is one mechanism to induce sebocyte apoptosis using isotretinoin, where Nelson demonstrates that isotretinoin is effective at reducing sebaceous gland size in acne.
Regarding the limitations of claim 2, where the casein kinase 1 is selected from the group including general formula I, formulas II-VI, D4476, IC261 and CKI7, are met as Mashhoon and Ben Neriah disclose IC261, CKI7 and compounds A14, A47, A51, A64, and A75 which read upon general formula I.
Concerning the limitation of claim 3, wherein the subject suffers from a sebaceous gland-related disorder, is met as Nelson explores the mechanism underlying treating patients with acne, a sebaceous gland disorder.
With respect to the limitation of claim 4, wherein the sebaceous gland-related disorder is a sebaceous gland dysfunction and/or a sebum overproduction-related disorder, is met as acne results from an over-production of sebum by sebaceous glands, which can clog hair follicles and lead to inflammation and pimples.
With regards to the limitations of claim 5, wherein the sebum overproduction-related disorder is induced by drug, infection, or hormones, are met as Zouboulis (2) teaches that sebaceous glands are regulated by hormone production, particularly in childhood to adolescence (abstract).
With concern to the limitations of claim 6, wherein the sebum overproduction-related disorder is selected from the group consisting of an acne, a seborrhea, a dermatitis, and an oily skin, are met as Nelson and Zouboulis (2) teach and explore treating the disorder of acne.
Regarding the limitation of claim 7, wherein the acne is a hormone-induced acne, is met as Zouboulis (2) teaches that acne in childhood to adolescence are associated with increased sebum excretion and is a major factor in the pathophysiology of acne vulgaris (abstract).
Concerning the limitation of claim 16, wherein the casein kinase 1 is casein kinase 1α, is met as Ben Heriah teaches inhibitors targeting CK1α (pg. 22).
Claims 8-10 are rejected under 35 U.S.C. 103 as being unpatentable over Zouboulis (1), Zhao, Nelson, Zouboulis (2), Mashhoon and Ben Neriah as applied to claims 1-7 and 16 above, and further in view of UCF Health (Seborrheic dermatitis and the link to hair loss, University of Central Florida, ucfhealth.com/our-services/dermatology/seborrheic-dermatitis-hair-loss-treatment/, 11 October 2020).
Zouboulis (1) disclose the use of isotretinoin to treat sebocytes through the mechanism of inducing sebocyte apoptosis through RXR binding and references Zhao who teaches that CK1α negatively regulates RXR and therefore sebocyte apoptosis. This is studied by Nelson, who explores the effect of isotretinoin on acne, expounded upon by Zouboulis (2), showing that isotretinoin is able to reduce sebaceous gland size. CK1 inhibitors IC261 and CKI7 are taught by Mashhoon whereas CK1α specific inhibitors are taught by Ben Neriah.
They do not, however, teach the sebum overproduction-related disorder due to dermatitis, wherein the dermatitis is an infection-induced dermatitis or a seborrheic dermatitis.
UCF Health addresses this paucity by teaching that seborrheic dermatitis, also called seborrheic eczema, is a chronic skin condition that predominately affects the scalp, damages hair follicles, and hinders hair growth, resulting from a fungal disease. The term seborrhea characterizes chronic inflammatory conditions that cause scaly skin and oily skin due to excessive sebum product by the sebaceous glands (pg. 1).
As such, it would have been prima facie obvious, to a person of ordinary skill in the art, before the effective filing date, to consider seborrheic dermatitis as a possible sebum overproduction-related disorder that could be treated by CK1α inhibition.
Regarding the limitation of claim 9, wherein the subject suffers from a hair loss, is met as UCF Health teaches that hair loss is closely associated with seborrheic dermatitis because increased sebum production can create irritation and inflammation on the scalp, which can cause intense itchiness, the reflexive scratching resulting in damaged follicles (pg. 1).
Concerning the limitations of claim 10, wherein the hair loss is a hair loss caused by nutritional deficiency, a drug-induced hair loss, a radiation-induced hair loss, a stress-induced hair loss, a genetic hair loss, an aging hair loss, or a disease-induced hair loss, are met as the hair loss associated with seborrheic dermatitis is disease-induced.
With respect to the limitation of claim 11, wherein the drug-induced hair loss is induced by a drug listed within the limitations, is met as UCF Health teaches that the antifungal agent, selenium sulfide, can treat seborrheic dermatitis by eliminating Malassezia yeast but has potential side effects including increased hair loss (pg. 3).
With regards to the limitation of claim 12, wherein the disease-induced hair loss is caused by an autoimmune disease, a thyroid disorder, a metabolic syndrome, an infection, or a cancer, is met as UCF Health teaches that seborrheic dermatitis is caused by infection of a fungal disease (pg. 1).
Claims 12-15 are rejected under 35 U.S.C. 103 as being unpatentable over Zouboulis (1), Zhao, Nelson, Zouboulis (2), Mashhoon and Ben Neriah as applied to claims 1-7 and 16 above, and further in view of Fricke et al. (Epidemiology and burden of alopecia areata: a systematic review, Clinical, Cosmetic and Investigational Dermatology 2015, 8, 397-403).
Zouboulis (1) disclose the use of isotretinoin to treat sebocytes through the mechanism of inducing sebocyte apoptosis through RXR binding and references Zhao who teaches that CK1α negatively regulates RXR and therefore sebocyte apoptosis. This is studied by Nelson, who explores the effect of isotretinoin on acne, expounded upon by Zouboulis (2), showing that isotretinoin is able to reduce sebaceous gland size. CK1 inhibitors IC261 and CKI7 are taught by Mashhoon whereas CK1α specific inhibitors are taught by Ben Neriah.
They do not, however, teach wherein the subject undergoing the method of claim 1 suffers from disease-induced hair loss caused by an autoimmune disorder.
Fricke overcomes this absence by teaching that alopecia areata is an autoimmune disorder that is characterized by patches of non-scarring alopecia affecting scalp and body hair. It is clinically heterogenous and unpredictable from natural history, with no preventative therapy or cure. It is the most prevalent autoimmune disorder and the second most prevalent hair loss disorder after androgenetic alopecia with the lifetime risk in the global population being approximately 2%. It is also associated with psychiatric and medical comorbidities including depression, anxiety, and several autoimmune disorders (abstract).
As such, it would be prima facie obvious, to a person of ordinary skill in the art, before the effective filing date, to consider patients who have the condition of alopecia areata, arising from an autoimmune disorder.
Regarding the limitation of claim 13, wherein the autoimmune disease is alopecia areata, lupus erythematosus, Sicca syndrome, scleroderma, Crohn’s disease, inflammatory bowel disease, or psoriasis, is met as Fricke teaches the condition of alopecia areata.
Concerning the limitation of claim 14, wherein the subject suffers from alopecia, is met as Fricke teaches the condition of alopecia areata, a species of the genus of alopecia.
With respect to the limitation of claim 15, wherein the alopecia is selected from the group consisting of androgenetic alopecia, alopecia areata, anagen effluvium, self-induced hair loss, telogen effluvium, and scarring alopecia, is met as Frick teaches the condition of alopecia areata.
Summary
Claims 1-16 are rejected under 35 U.S.C. 103.
Conclusion
No claims are allowed.
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/ALLEN CHAO/Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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