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 .
Application Status
The amendment filed on 1/27/2026 in response to the Non-Final Rejection of 9/29/2025 is acknowledged and has been entered. Claims 16-27, 30-32 and 36 are currently pending and under consideration.
Information Disclosure Statement
The information disclosure statement filed on 8/29/2025 has been considered except where lined through.
Response to Amendment
The declaration under 37 CFR 1.132 filed 1/27/2026 by Christine Bodemer is insufficient to overcome the rejection of claims 16-27, 30-32 and 36 under 35 U.S.C. 103 as being unpatentable over Arkin et al. (US11,633,399, 2023-04-25) in view of Kenner-Bell et al. (J. Am. Acad. Dermatol 2010, 63:2, e58-e59), Duchatelet et al. (Orphanet Journal of Rare Diseases (2015), 10:33) and Koren et al. (US2023/0255884A1, 2023-08-17) and Bodemer et al. (US20210393632A1, 12/23/2021, priority to EP18306306.4 filed 10/4/2018) in view of Arkin et al. (US11,633,399, 2023-04-25) in view Duchatelet et al. (Orphanet Journal of Rare Diseases (2015), 10:33) and Koren et al. (US2023/0255884A1, 2023-08-17)as set forth in the last Office action. In response to the rejection, the Declarant asserts that patient care management for keratoderma, such as Olmested syndrome, is extremely heavy and unsatisfactory citing a passage from Duchatelet “Until now, treatments either topical or systemic only offer temporary partial symptomatic relief of pain and fissures by reducing the thickness keratotic palmoplantar skin lesions (see page 8, “Management including treatment” section”. Moreover, the Declarant teaches that the specific treatment of young patients is particularly problematic, wherein oral (and more generally systemic) administration of an EGFR inhibitor such as erlotinib, as taught by Kenner-Bell) can be accompanied by numerous side effects such as rash (observed in the majority of patients), diarrhea, loss of appetite, fatigue and partial hair loss, especially in young patients. Accordingly, the Declarant assert that the present invention demonstrates that a topical formulation allows efficient absorption of erlotinib, clinically reduces keratoderma symptoms, and improves patients’ quality of life.
In response to Declarants arguments regarding patient care management for keratoderma, such as Olmsted syndrome, the Examiner acknowledges Declarants citation of Duchatelet. However, the Examiner recognizes that, as taught by Kenner-Bell, oral administration of erlotinib has been previously shown to be effective in treating Olmsted syndrome. Declarant is reminded that Obviousness does not require absolute predictability, but at least some degree of predictability is required (see MPEP 2143.02): Regarding Declarants’ assertion that specific treatment of young patients is particularly problematic, the examiner recognizes that Declarant has not provided any factual evidence showing that young patients are particularly problematic compared to adult patients. Regarding the specific side-effects, Arkin et al. acknowledges cutaneous side-effects reported in the literature are the result of oral (systemic) treatment with EGFR inhibitors, wherein non-oral administration would avoid the systemic side effects (see for example, Column 6, lines 7-25). Lastly, while the specification provides numerous examples of the topical use of erlotinib in treating a Keratoderma, including in patients younger than age 15, these appear to be prophetic examples and do not provide any actual results differentiating the two patient populations (e.g. younger than 15 vs. older than 15).
Rejections Maintained
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
Claim(s) 16-27, 30-32 and 36 remain rejected under 35 U.S.C. 103 as being unpatentable over Arkin et al. (US11,633,399, 2023-04-25) in view of Kenner-Bell et al. (J. Am. Acad. Dermatol 2010, 63:2, e58-e59), Duchatelet et al. (Orphanet Journal of Rare Diseases (2015), 10:33) and Koren et al. (US2023/0255884A1, 2023-08-17).
Arkin et al. teach compositions and methods of treating skin or mucosal disorder by administering compositions comprising at least one EGFR inhibitor, such as topical compositions comprising erlotinib (abstract). With regards to the skin or mucosal disorders, Arkin et al. teach that skin or mucosal disorders include, but are not limited to, psoriasis, palmoplantar psoriasis, and acquired palmoplantar keratosis (Column 2, lines 58-62). For example, Arkin et al. teach a method of treatment of psoriasis by topical administration to the subject a composition comprising a therapeutically effective amount of erlotinib in a concentration of from about 3% to 5% w/w (claim 1 of Arkin et al.). Moreover, the US Patent teaches that the method comprises one or twice daily topical applications of therapeutically effective amounts of said composition to the skin portion of the subject affected by the skin disorder (claim 15 of the US Patent). With regards to the composition, the US Patent teaches that the composition further comprises at least one penetration enhancer such as ethanol or a polyethylene glycol, wherein the topical composition is in the form of a cream, ointment, gel, lotion, spray, shampoo, patch or a foam (column 8, lines 55-62 and column 10, lines 1-3). Lastly, the US Patent teaches that the compositions of the invention when administered topically or intralesional do not induce or induces reduced cutaneous side-effects as compared with the same EGFR inhibitor amount administered in different methods/routes (column 19, lines 1-5).
Arkin et al. does not specifically select palmoplantar keratoderma, specifically Olmstead syndrome (Palm and sole) as the genetic skin disorder, specifically select erlotinib as the EGFR inhibitor, identify the patient as being a child of less than 15 years old or include the composition in a woven or non-woven support such as sock or a glove.
Kenner-Bell et al teach the use of the epidermal growth factor receptor (EGFR) inhibitor erlotinib in a patient with Olmstead syndrome (1st column, paragraph entitled To the Editor). With regards to the patient, the article teaches that the patient was a 31 year old woman whom had exquisitely tender palmoplantar Keratoderma with flexion contractures and crippling deformity since childhood and further, has been unable to walk for approximately 15 years (page e58, last paragraph bridging 1st and 2nd column). With regards to the erlotinib, the article teaches that the patient initially received 100 mg daily, which was increased to 150 mg daily which further improved the keratoderma, increased range of motion, and enabled her to walk without significant discomfort (page e58, 2nd column last full paragraph). Specifically, the article teaches that by 110 days after initiation of erlotinib, the thickening of the palms and soles was dramatically reduced (page e59, Fig 2 showing a picture of the hands).
Duchatelet et al. teach that Olmsted syndrome (OS) is a rare genodermatosis belonging to the heterogenous group of palmoplantar keratoderma (PPK) (Introduction). Specifically, Duchatelet et al. teach that the disease starts usually at birth, in neonatal period or in early childhood, when the child starts to walk and grasp, and worsens over time (Clinical Description).
Koren et al. teach that while transdermal or dermal administration of active pharmaceutical ingredients including gels, creams, sprays, lotion and patches are known, there a numerous disadvantages in their use such as being too messy or greasy resulting in a significant amount of the formulation transferred away from the skin, as well as, repeated applications of the formulation multiple times a day to maintain efficacy (paragraph 0003). Moreover, Koren et al. teach that a disadvantage of patch formulation, which is due to their inflexibility, is that there are areas of the body wherein a patch does not adhere well, for example, on joint areas or areas having skin to skin contact such as between fingers and toes (paragraph 0003). According, Koren et al. teach dry-non-occlusive, pharmaceutical fibrous structures finished with an active pharmaceutical ingredient (paragraph 0007). With regards to the fibrous structures, Koren et al. teach that fibrous structures are structures composed of loose fibers, yarns or fabric such as woven or non-woven fabrics (paragraph 0053). Moreover, Koren et al. teach a method of treating a condition comprising applying to the intact skin of a body part of a subject an item of clothing, wherein the item of clothing comprises a dry, non-occlusive, fibrous structure which has been finished with an active pharmaceutical ingredient (Paragraph 0075). With regards to the item of clothing, Koren et al. teaches that the item of clothing includes, but is not limited to, a sock or glove (paragraph 0076).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to modify the method taught by Arkin et al. to specifically select palmoplantar keratoderma, specifically Olmstead syndrome (palm or feet) as the genetic skin disorder, specifically select erlotinib as the EGFR inhibitor and include children less than 15 years old. One of ordinary skill in the art would have been motivated to make such a modification, with a reasonable expectation of success, because:
-Kenner-Bell et al teach the benefits of the epidermal growth factor receptor (EGFR) inhibitor erlotinib in a patient with Olmstead syndrome (type of inherited palmoplantar keratoderma),
-Kenner-Bell further teaches that the patient has had this disorder since childhood and has not walked for almost 15 years (subject was 31, so has not work since age 16),
-Kenner-Bell further teaches Olmstead syndrome impacts palms and soles of a patient and
- Duchatelet et al. teach that Olmstead syndrome starts usually at birth, in neonatal period or in early childhood, when the child starts to walk and grasp, and worsens over time.
Moreover, it would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to modify the composition taught by Arkin et al. so as to include it within a woven or non-woven fibrous structure such as a glove or a sock in view of the teachings of Koren et al. . One would have been motived to make such as modification with a reasonable expectation of success because:
Koren et al. teaches numerous disadvantages of known topical dermal and transdermal formulations and provides a method of treating a condition comprising applying to the intact skin of a body part of a subject an item of clothing, wherein the item of clothing comprises a dry, non-occlusive, fibrous structure which has been finished with an active pharmaceutical ingredient
In response to the rejection, Applicants provide arguments that mirror those already set forth within the declaration, relating to the patent care management for keratoderma and treatment of young patients which have been argued above. In addition, Applicants argues that although Arkin teaches the topical administration of EGFR inhibitors for the treatment skin or mucosal disorders, Arkin fails to provide a single working example where a skin disorder, let alone a palmoplantar keratoma, would be actually treated by means of a topical EGFR inhibitor administration. Applicants further argues each reference individually ultimately concluding that there is nothing that would have motivated one skilled in the art to specifically treat young keratoderma patients, let alone by means of topical erlotinib administration.
These arguments have been carefully considered, but are not found persuasive.
The Examiner has addressed Applicants arguments relating to the Declaration above and are incorporated herein. Regarding Applicants arguments pertaining to the lack of examples in Arkin, the Examiner recognizes that “When the reference relied on expressly anticipates or makes obvious all of the elements of the claimed invention, the reference is presumed to be operable. Once such a reference is found, the burden is on applicant to rebut the presumption of operability. In re Sasse, 629 F.2d 675, 207 USPQ 107 (CCPA 1980).” A prior art reference provides an enabling disclosure and thus anticipates a claimed invention if the reference describes the claimed invention in sufficient detail to enable a person of ordinary skill in the art to carry out the claimed invention; "proof of efficacy is not required for a prior art reference to be enabling for purposes of anticipation." Impax Labs. Inc. v. Aventis Pharm. Inc., 468 F.3d 1366, 1383, 81 USPQ2d 1001, 1013 (Fed. Cir. 2006) (citing Rasmusson v. SmithKline Beecham Corp., 413 F.3d 1318, 1326, 75 USPQ2d 1297, 1302 (Fed. Cir. 2005)). See MPEP 2121. Thus, since Applicants have not provided any specific proof that the reference is not enabled, these arguments are not persuasive. Regarding Applicants arguments pertaining to the reference individually, the examiner recognizes that one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). As discussed above, it would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to modify the method taught by Arkin et al. to specifically select palmoplantar keratoderma, specifically Olmstead syndrome (palm or feet) as the genetic skin disorder, specifically select erlotinib as the EGFR inhibitor and include children less than 15 years old. One of ordinary skill in the art would have been motivated to make such a modification, with a reasonable expectation of success, because:
-Kenner-Bell et al teach the benefits of the epidermal growth factor receptor (EGFR) inhibitor erlotinib in a patient with Olmstead syndrome (type of inherited palmoplantar keratoderma),
-Kenner-Bell further teaches that the patient has had this disorder since childhood and has not walked for almost 15 years (subject was 31, so has not work since age 16),
-Kenner-Bell further teaches Olmstead syndrome impacts palms and soles of a patient and
- Duchatelet et al. teach that Olmstead syndrome starts usually at birth, in neonatal period or in early childhood, when the child starts to walk and grasp, and worsens over time.
Note: As discussed in the response to the declaration, while the specification provides numerous examples of the topical use of erlotinib in treating a Keratoderma, including in patients younger than age 15, these appear to be prophetic examples and do not provide any actual results differentiating the two patient populations (e.g. younger than 15 vs. older than 15).
Claim(s) 16-27, 30-32 and 36 remain rejected under 35 U.S.C. 103 as being unpatentable over Bodemer et al. (US20210393632A1, 12/23/2021, priority to EP18306306.4 filed 10/4/2018) in view of Arkin et al. (US11,633,399, 2023-04-25) in view Duchatelet et al. (Orphanet Journal of Rare Diseases (2015), 10:33) and Koren et al. (US2023/0255884A1, 2023-08-17).
The PG Pub claims a method of treating keratoderma in a patient in need thereof comprising administering to the patient a therapeutically effective amount of an EGFR inhibitor (claim 1). The PG Pub further claims that the patient suffers from palmoplantar keratoderma (claims 2-3, 13-15), specifically Olmsted syndrome (claim 4), the EGFR inhibitor is erlotinib (claims 8-9), the EGFR inhibitor is administered in a topical formulation (claim 12), and the patient is 15 years old (paragraph 0035).
The PG Pub does not claim that erlotinib is in an amount ranging from about 0.01 to about 10% by weight of the total weight of the composition or that the erlotinib is administered to the palms and/or feet of the patient or that the composition is within a woven or non-woven support such as a sock or glove or that the formulation comprises a penetration enhancer or that the patient is younger than 15 years old.
Arkin et al. teach compositions and methods of treating skin or mucosal disorder by administering compositions comprising at least one EGFR inhibitor, such as topical compositions comprising erlotinib (abstract). With regards to the skin or mucosal disorders, Arkin et al. teach that skin or mucosal disorders include, but are not limited to, psoriasis, palmoplantar psoriasis, and acquired palmoplantar keratosis (Column 2, lines 58-62). For example, Arkin et al. teach a method of treatment of psoriasis by topical administration to the subject a composition comprising a therapeutically effective amount of erlotinib in a concentration of from about 3% to 5% w/w (claim 1 of Arkin et al.). Moreover, the US Patent teaches that the method comprises one or twice daily topical applications of therapeutically effective amounts of said composition to the skin portion of the subject affected by the skin disorder (claim 15 of the US Patent). With regards to the composition, the US Patent teaches that the composition further comprises at least one penetration enhancer such as ethanol or a polyethylene glycol, wherein the topical composition is in the form of a cream, ointment, gel, lotion, spray, shampoo, patch or a foam (column 8, lines 55-62 and column 10, lines 1-3). Lastly, the US Patent teaches that the compositions of the invention when administered topically or intralesional do not induce or induces reduced cutaneous side-effects as compared with the same EGFR inhibitor amount administered in different methods/routes (column 19, lines 1-5).
Duchatelet et al. teach that Olmsted syndrome (OS) is a rare genodermatosis belonging to the heterogenous group of palmoplantar keratoderma (PPK) (Introduction). Specifically, Duchatelet et al. teach that the disease starts usually at birth, in neonatal period or in early childhood, when the child starts to walk and grasp, and worsens over time (Clinical Description).
Koren et al. teach that while transdermal or dermal administration of active pharmaceutical ingredients including gels, creams, sprays, lotion and patches are known, there a numerous disadvantages in their use such as being too messy or greasy resulting in a significant amount of the formulation transferred away from the skin, as well as, repeated applications of the formulation multiple times a day to maintain efficacy (paragraph 0003). Moreover, Koren et al. teach that a disadvantage of patch formulation, which is due to their inflexibility, is that there are areas of the body wherein a patch does not adhere well, for example, on joint areas or areas having skin to skin contact such as between fingers and toes (paragraph 0003). According, Koren et al. teach dry-non-occlusive, pharmaceutical fibrous structures finished with an active pharmaceutical ingredient (paragraph 0007). With regards to the fibrous structures, Koren et al. teach that fibrous structures are structures composed of loose fibers, yarns or fabric such as woven or non-woven fabrics (paragraph 0053). Moreover, Koren et al. teach a method of treating a condition comprising applying to the intact skin of a body part of a subject an item of clothing, wherein the item of clothing comprises a dry, non-occlusive, fibrous structure which has been finished with an active pharmaceutical ingredient (Paragraph 0075). With regards to the item of clothing, Koren et al. teaches that the item of clothing includes, but is not limited to, a sock or glove (paragraph 0076).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to modify the formulation taught by the PG Pub, to include 3% to 5% erlotinib and a penetration enhancer such as ethanol, and further apply the formulation to the sight of the disorder such as the palm and/or feet in view of the teachings of Arkin et al.. One of ordinary skill in the art would have been motivated to make such a modification, with a reasonable expectation of success, because:
- Arkin et al. teaches a topical composition for treating similar disorder order, e.g. acquired palmoplantar keratosis, using a formulation comprising 3% to 5% w/w erlotinib and a penetration enhancer; and further suggests applying the composition to the part of the skin effected by the disorder.
Moreover, it would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to modify the method taught by the PG Pub to include patents less than 15 years old in view of the teachings Duchatelet et al.. One of ordinary skill in the art would have been motivated to make such a modification, with a reasonable expectation of success, because:
- Duchatelet et al. teach that Olmstead syndrome starts usually at birth, in neonatal period or in early childhood, when the child starts to walk and grasp, and worsens over time.
Lastly, it would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to modify the composition taught by the PG Pub so as to include the composition within a woven or non-woven fibrous structure such as a glove or a sock in view of the teachings of Koren et al. . One would have been motived to make such as modification with a reasonable expectation of success because:
Koren et al. teaches numerous disadvantages of known topical dermal and transdermal formulations and provides a method of treating a condition comprising applying to the intact skin of a body part of a subject an item of clothing, wherein the item of clothing comprises a dry, non-occlusive, fibrous structure which has been finished with an active pharmaceutical ingredient
In response to the rejection, Applicants provide arguments that mirror those already set forth above and have been carefully considered, but are not found persuasive for the reasons set forth above and incorporated herein.
Conclusion
No Claim is allowed.
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 BRANDON J FETTEROLF whose telephone number is (571)272-2919. The examiner can normally be reached M-F 6AM-4PM.
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/BRANDON J FETTEROLF/Primary Examiner, Art Unit 1626