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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 5/26/2026 has been entered.
Claims 16-25, 27, 30-32 and 36 are currently pending and under consideration.
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) 16-25, 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 walked 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 argue the formulation of a topical composition that would allow for the efficient transdermal delivery of erlotinib could not, prior to the effective filing date of the instantly claimed invention, be considered obvious to the skilled person. In particular, Applicants contend that the stabilization of erlotinib in topical formulations was known to be difficult. For example, Applicants argue that erlotinib significantly degrades under oxidative stress and under alkaline conditions, which are conditions occurring in topical formulations, and even more when the compositions is comprised and applied in a woven or non-woven fabric. Applicants further cite Han et al. (“Pharmaceutical Formulation Technology”, Harbin Engineering University Press, August 2008, the first addition, pages 234-258- cited in an IDS) as outlining the use limitations of transdermal drug delivery systems, emphasizing that not all drugs (only a few drugs) are suitable for development into transdermal patches. Moreover, Applicants assert that prior to the effective filing date of the instantly claimed invention, no approved topical, dermatological or transdermal formulations existed, despite clinical interest in local EGFR inhibition. Regarding Arkin, Applicants argue that although Arkin teaches the topical administration of EGFR inhibitors for the treatment of skin or mucosal disorders, Arkin fails to provide a single working Example wherein a skin disorder, let alone a palmoplantar keratoderma, would actually be treated by means of a topical EGFR inhibitor administration. Applicants further maintain the previous arguments that the successful treatment of young patients suffering from keratoderma by means of topical erlotinib administration represents a major breakthrough that cannot be derived from the cited prior art. Regarding the other references used in the rejection, Applicants address these reference individually as not teaching topical administration of erlotinib.
These arguments have been carefully been considered, but are not found persuasive.
In response to these arguments, the examiner acknowledges and does not disagree with Applicants contention that prior to the effective filing date of the instantly claimed invention, no approved topical, dermatological or transdermal formulations existed. However, the examiner recognizes that Arkin et al. constitutes prior art having an effective filing date of at least 01/08/2020. Accordingly, topical formulations of erlotinib did exist. Regarding Applicants arguments regarding the stability issues of erlotinib in topical formulations. It is noted that Applicants have not provided any factual evidence to show that erlotinib degrades “even more” when the composition is comprised and applied in a woven or non-woven structure. Regarding Applicants arguments pertaining to Arkin et al., 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). See also MPEP § 716.07. See also In re Antor Media Corp., 689 F.3d 1282, 103 USPQ2d 1555 (Fed. Cir. 2012). Specifically, in In re Antor Media Corp., the court stated:
"Consistent with the statutory framework and our precedent, we therefore hold that, during patent prosecution, an examiner is entitled to reject claims as anticipated by a prior art publication or patent without conducting an inquiry into whether or not that prior art reference is enabling. As long as an examiner makes a proper prima facie case of anticipation by giving adequate notice under § 132, the burden shifts to the applicant to submit rebuttal evidence of nonenablement."
In re Antor Media Corp., 689 F.3d at 1289, 103 USPQ2d at 1559.
Moreover, 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.
Lastly, as commented on in the prior office action, 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).
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 walked 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.
Regarding Applicants arguments pertaining to treatment of keratoderma in young patients, these arguments have been previous addressed in the Final-Rejection of 2/25/2026 (see page 3, response to the declaration) and are incorporated herein.
Claim(s) 16-25, 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.
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey S Lundgren can be reached at 571-272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BRANDON J FETTEROLF/Primary Examiner, Art Unit 1626
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