Detailed Action
The present office action is in response to the amendments filed on 02 Nov 2025.
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 .
Status
Claims 1-3, 9, 12, 16, 18-20, 22, 25-30, 33, and 35-39 of the pending application have been examined on the merits. Claim 32 remains withdrawn. Acknowledgement is made of the amendments filed 02 Nov 2025. Acknowledgement is made of the cancellation of claim 4-8, 10-11, 13-15, 17-19, 21, 23-24, 31, and 34.
Priority
Applicants identify the instant application, Serial #: 17/521,884, filed 09 Nov 2021, as a National Stage Entry of International Patent Application #: PCT/IL2020/051153, filed 05 Nov 2020, which claims priority from U.S. Provisional Application #: 62/931,252, filed 06 Nov 2019.
Response to Applicant Arguments
Acknowledgement is made of the amendments filed 02 Nov 2025.
The rejection of claims 4-8, 10-11, 13-15, 17-19, 21, 24, 31, and 34 under 35 U.S.C. § 103 is rendered moot following the cancellation of the claims.
The rejection of claims 1-3, 9, 12, 16, 18-20, 22, 25-30, 33, and 35-39 is rendered moot following applicant amendments. However, a new rejection under 112(a) (see below) has been made. This rejection is necessitated by applicant amendments.
Examiner Interpretation
The independent claim, claim 1, of the instant application includes the limitation of treating, preventing, or alleviating PPK or Olmsted syndrome by “oral debridement of affected PPK surface area or Olmsted syndrome surface area…wherein the oral debridement consists of oral administration of at least one EGFR inhibitor.” Applicant has no definition of “debridement” included in their specification and so examiner is taking the commonly held definition of debridement, as evidenced by Anghel et al. (Plast. Reconstr. Surg, 2016, 138:82S-93S), which teaches that the clinical definition of debridement is the removal of nonviable or contaminated tissue that impedes normal tissue growth (pg. 82S, column 1). Examiner has interpreted “oral debridement” to mean the removal of nonviable or contamination tissue within the oral cavity by applying an EGFR inhibitor to the effected tissue in the oral cavity.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-3, 9, 12, 16, 18-20, 22, 25-30, 33, and 35-39 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
To be enabling, the specification of the patent application must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fd. Cir. 1993). Explaining what is meant by "undue experimentation," the Federal Circuit has stated that:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996). As pointed out by the court in In re Angstadt, 537 F.2d 498 at 504 (CCPA 1976), the key word is "undue", not "experimentation".
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 wherein, citing Ex parte Forman, 230 USPQ 546 (Bd. Apls. 1986) at 547 the court recited eight factors:
the quantity of experimentation necessary,
the amount of direction or guidance provided,
the presence or absence of working examples,
the nature of the invention,
the state of the prior art,
the relative skill of those in the art,
the predictability of the art, and
the breadth of the claims
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
The nature of the invention, state and predictability of the art, and relative skill of those in the art
The invention relates to methods of treating, preventing, or alleviating PPK or Olmsted syndrome comprising administering an oral debridement agent (where the oral debridement agent is at least one EGFR inhibitor) and topical administration of erlotinib following the oral debridement step.
The relative skill of those in the art is high, generally that of an M.D. or Ph.D. The artisan using Applicant’s invention would generally be a physician with a M.D. degree and several years of experience.
The factor is outweighed, however, by the unpredictable nature of the art. It is well established that “the scope of enablement varies with the degree of unpredictability of the factors involved” and physiological activity is considered to be an unpredictable factor. See In re Fisher, 166 USPQ 18, at 24 (In cases involving unpredictable factors, such as most chemical reactions and physiological activity, the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved); Nationwide Chemical Corporation, et. al. v. Wright, et. al., 192 USPQ 95 (one skilled in chemical and biological arts cannot always reasonably predict how different chemical compounds and elements might behave under varying circumstances); Ex parte Sudilovsky 21 USPQ2d 1702 (Applicant’s invention concerns pharmaceutical activity.); In re Wright 27 USPQ2d 1510 (the physiological activity of RNA viruses was sufficiently unpredictable that success in developing specific avian vaccine was uncertain).
As illustrative of the state of the art for keratoderma treatment, the examiner cites Pukhalskaya et al. (New and Emerging Entities in Dermatology and Dermatopathology, 2021, pg. 459-465), hereinafter Pukhalskaya, Bukhari et al. (Case Rep Dermatol, 2019, 11:292-296; cited in the office action mailed 01/24/2025), hereinafter Bukhari, Foundation for Icthyosis and Related Skin Types (retrieved from https://web.archive.org/web/20160922042880/http://www.firstskinfoundation.org/, accessed 11/22/2024; provided in the office action mailed 01/24/2025), hereinafter FIRST, Bodemer et al. (Bri J Dermatol, 2021, 184:939-400), hereinafter Bodemer, and Chen et al. (Bri J Dermatol, 2018, 178:129-131; provided in the office action mailed 01/24/2025), hereinafter Chen. As illustrative of the state of the art for debridement techniques, the examiner cites Anghel et al. (Plast. Reconstr. Surg, 2016, 138:82S-93S), hereinafter Anghel.
Pukhalskaya, Bukhari, FIRST, Bodemer, and Chen represent the state of the art for treatment of PPK. Pukhalskaya, cited for evidence, teaches that tacalcitol ointment, 5-fluorouracil cream, ammonium lactate, tretinoin, and mechanical debridement are known to treat spiny keratoderma (pg. 463). Bukhari, cited for evidence, further teaches that topical karatolytics, liquid nitrogen, PUVA, systemic or topical retinoids, systemic acitretin, etretinate or alitretinoin, and topical steroids can be used to treat Type 1 PPPK (pg. 294). FIRST, cited for evidence, teaches that in addition to the treatments described by Pukhalskaya and Bukhari, PPK treatment may be helped by dermabrasion and carbon dioxide laser treatment and that difficult to treat keratoderma might be treated by excision of hyperkeratotic skin followed by grafts (pg. 5). However, there is no art which teaches a person of skill in the art how to prevent PPK or Olmsted syndrome. Further, there is nothing in the art that teaches or suggests that an EGFR inhibitor may be used for oral debridement. It has even been reported in the art that olmutinib, an EGFR inhibitor, can cause PPK, as evidence by Chen (whole document). Based on the art of treating PPK, a skilled artisan would not be sure how to perform debridement using an EGFR inhibitor.
The artisan may also look to general debridement procedures for ideas of how to treat PPK and Olmsted syndrome by administering an oral EGFR inhibitor for debridement. Anghel represents the state of the art for debriding agents. Anghel, cited for evidence, teaches that the methods of wound debridement can be separated into mechanical, biologic, technical, and surgical methods (pg. 85S, column 2). EGFR inhibition could possibly be construed to fall into the biologic category, however, there is no mention of such therapy in Anghel. There was no reference found by the examiner which includes EGFR inhibition as a viable method of debridement. The artisan would have no guidance from the state of the art which would allow them to treat PPK or Olmsted syndrome by administering an oral EGFR inhibitor for debridement.
The amount of direction or guidance provided and the presence or absence of working examples
The specification provides data about the compositions containing erlotinib for the topical administration step and further details how a study would be performed to test the topical compositions. However, there are no examples describing how a person having skill in the art would administer an oral EGFR inhibitor for debridement as a means of treating, preventing, or alleviating PPK or Olmsted syndrome.
The specification provides no particular direction or guidance for determining the particular administration regimens (e.g., timing, administration routes, etc.) necessary to treat, prevent, or alleviate PPK or Olmsted syndrome with an oral EGFR inhibitor as a debriding agent. At best, the specification provides that “the debridement step…comprises oral administration of at least one EGFR inhibitor” (pg. 6, lines 25-26). While the specification provides references for other debriding techniques, there are no incorporated patents or patent applications describing the use of EGFR inhibitors as debriding agents.
The quantity of experimentation necessary
Because of the known unpredictability of the art (as discussed above) and in the absence of experimental evidence commensurate in scope with the claims, the skilled artisan would not accept that an oral EGFR inhibitor could be predictably used as a debriding agent.
Genentech Inc. vs. Nova Nordisk states, "[A] patent is not a hunting license. It is not a reward for a search but a compensation for its successful conclusion and 'patent protection' is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable" (42 USPQ 2d 1001, Fed. Circuit 1997).
As noted above, none of the experimentation provided is drawn to the administration of an oral EGFR inhibitor as a debriding agent and a topical EGFR inhibitor for the treatment, prevention, or alleviation of PPK or Olmsted syndrome. A review of the state of the art fails to reveal that oral EGFR inhibitors are useful as a therapeutic for the debridement of any dermatological disease, including PPK and Olmsted syndrome. This is undue experimentation given the limited guidance and direction provided by the application.
Accordingly, the instant claims do not comply with the enablement requirement of 35 U.S.C. 112(a), since to practice the claimed invention a person of ordinary skill in the art would have to engage in undue experimentation, with no assurance of success.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-3, 9, 12, 16, 18-20, 22, 25-30, 33, and 35-39 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 includes the limitation of “oral debridement of affected PPK surface area or Olmsted syndrome surface area…” However, PPK and Olmsted syndrome have not been reported to affect surface areas in the oral cavity and it is unclear how a person of ordinary skill in the art would treat PPK or Olmsted syndrome by debriding the oral cavity. Claims 2-3, 9, 12, 16, 18-20, 22, 25-30, 33, and 35-39 are rejected for failing to remedy this deficiency. Applicant may overcome this rejection by amending the independent claim to clarify how oral debridement by administration of an EGFR inhibitor treats the surface area affected PPK or Olmsted syndrome.
Claim 1 includes the limitation, “wherein the oral administration consists of oral administration of at least one EGFR inhibitor…” The phrase, “consists of,” is a closed list. See MPEP § 2111.03(II). However, “at least one EGFR inhibitor” implies there may be an unknown number of EGFR inhibitors administered as debriding agents, indicating an open-ended list. The combination of the closed list and open-ended list makes the claim indefinite. Claims 2-3, 9, 12, 16, 18-20, 22, 25-30, 33, and 35-39 are rejected for failing to remedy this deficiency. Appropriate correction is required.
Claim 38 recites the limitation "wherein the debridement step and topical administration are sequentially, concomitantly, or the topical administration is only applied after the debridement step is complete." There is insufficient antecedent basis for this limitation in the claim. Claim 38 depends on claim 1, and claim 1 limits the topical administration step (b) to only occurring after the debridement step (a). Claim 1 does not allow for step (a) to occur after step (b), which is implied by claim 38’s limitation of “sequentially.” Claim 1 also does not allow for step (a) to occur “concomitantly” as step (b). Thus, claim 38 lacks antecedent basis. Appropriate correction is required.
Conclusion
No claim is allowed. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jonathan D. Mahlum whose telephone number is (703)756-4691. The examiner can normally be reached 8:30 AM - 5:00 PM ET, M-F.
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, Andrew Kosar can be reached on (571) 272-0913. 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.
/J.D.M./Examiner, Art Unit 1625
/Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625