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
Claims 1-2 and 6-14 are pending in the present application.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 02/05/2026 has been entered.
Previous Claim Rejections - 35 USC § 103
Claims 1-14 were previously rejected under 35 U.S.C. 103 as being unpatentable over Clinical Trial NCT02762084 (PellePharm Inc, study closed 07/23/2020; references from V10 study update 07/08/2020; henceforth NCT ‘084), in view of Epstein (Epstein, Ervin H., et al. "Hedgehog pathway inhibition by topical patidegib to reduce BCC burden in patients with basal cell nevus (Gorlin) syndrome." (2018): e21626-e21626.).
Applicant has traversed the previous rejection on several grounds.
The Examiner has considered the traversal fully but must disagree for the reasons which are set forth below.
The previous rejection is maintained in an amended form to address Applicant’s traversal.
Applicant has traversed the previous rejection on grounds NCT’084 and Epstein do not teach or suggest “(i) restricting treatment to a PTCH1-positive selected subject, and (ii) requires pre-therapy confirmation of a PTCH1 mutation as a mandatory prerequisite for eligibility, as required by amended claim 1.” See p.5, last paragraph of Applicant’s Remarks filed 02/05/2026.
A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989). See also Upsher-Smith Labs. v. Pamlab, LLC, 412 F.3d 1319, 1323, 75 USPQ2d 1213, 1215 (Fed. Cir. 2005) (reference disclosing optional inclusion of a particular component teaches compositions that both do and do not contain that component); Celeritas Technologies Ltd. v. Rockwell International Corp., 150 F.3d 1354, 1361, 47 USPQ2d 1516, 1522-23 (Fed. Cir. 1998). See MPEP 2123.
NCT’ 084 requires where “subject must meet diagnostic criteria for basal cell nevus syndrome (BCNS) including major criterion #3a plus one additional major criterion” and further lists “PTCH1 gene mutation in normal tissue” as a major criterion, would motivate one of skill in the art to at least assess whether subjects meet the criterion. Applicant’s assertion that NCT ‘084 does not teach or suggest limiting treatment to PTCH-mutated patients in not supported by the Inclusion Criteria in the Clinical Study Protocol.
The NCT ‘084 reference does not teach away from a method of treatment of Gorlin syndrome patients having the PTCH1 mutation at the time of therapy. The Clinical Study Protocol of the NCT ‘084 trial discloses where one of the major inclusion criteria for patients of the study is PTCH1 gene mutation in normal tissue. See page 8 of the Clinical Study Protocol attached herewith.
The present claims do not exclude an embodiment of a method of treatment and/or prevention of basal cell carcinoma (BCC) lesions in a patient suffering from Gorlin syndrome where one of ordinary skill in the art performs a general screening of all participants for mutations and subsequently treats each participant with 2% or 4% patidegib gel, regardless of mutation status.
Applicant further traverses the rejection on grounds “The fact that a PTCH1-positive subgroup exists within a broader group treated in the art does not teach or suggest the claimed restriction to a PTCH1-positive selected subject with confirmed PTCH1 mutation prior to initiation of therapy. The cited references do not teach a motivation to implement PTCH1-based screening and selection as a prerequisite to topical patidegib treatment, nor do they teach that such selection is critical to efficacy.”. See p.7, first paragraph.
Conclusive proof of efficacy is not required to show a reasonable expectation of success. See MPEP 2143.02, Section I. OSI Pharm., LLC v. Apotex Inc., 939 F.3d 1375, 1385, 2019 USPQ2d 379681 (Fed. Cir. 2019) ("To be clear, we do not hold today that efficacy data is always required for a reasonable expectation of success. Nor are we requiring ‘absolute predictability of success.’"); Acorda Therapeutics, Inc. v. Roxane Lab., Inc., 903 F.3d 1310, 1333, 128 USPQ2d 1001, 1018 (Fed. Cir. 2018) ("This court has long rejected a requirement of ‘[c]onclusive proof of efficacy’ for obviousness." (citing to Hoffmann-La Roche Inc. v. Apotex Inc., 748 F.3d 1326, 1331 (Fed. Cir. 2014); PharmaStem Therapeutics, Inc. v. ViaCell, Inc., 491 F.3d 1342, 1364 (Fed. Cir. 2007); Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1364, 1367–68 (Fed. Cir. 2007) (reasoning that "the expectation of success need only be reasonable, not absolute")).
The prior art need not teach, suggest or disclose where the method of treatment and/or prevention of BCC lesion is 100% effective in patients with Gorlin PTCH1 mutation. The fact the present claims encompass treatment as well as prevention means one of ordinary skill in the art practicing the method of the prior art would entail administration to a patient population embraced by the instant claims, Gorlin syndrome subjects carrying the PTCH1 genetic mutation prior to the initiation of therapy. The existence of the criterion to make the subgroup, as well as the subgroup itself, provides the suggest of treating at least one member of the group, a Gorlin syndrome patient carrying the PTCH1 gene mutation in normal tissue.
It is noted that the features upon which Applicant relies (e.g. a motivation to implement PTCH1-based screening and selection as a prerequisite to topical patidegib treatment) are not recited in the rejected claims and, therefore, these features do not carry any weight in terms of an obviousness analysis. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). The present claims recite treating BCC lesions in "a patient" not multiple patients. As it would have been obvious to treat and/or prevent BCC lesions in at least one Gorlin syndrome patient, the present claim are obvious.
Applicant alleges “the failure of the Phase 3 clinical trial demonstrates that one of ordinary skill in the art would not have had a reasonable expectation of success in treating Gorlin syndrome patients with topical patidegib without mandatory PTCH1 screening. Furthermore, the unexpected results disclosed in the specification establish that topical patidegib is effective only in PTCH1-positive Gorlin patients, which is contrary to the known efficacy of oral hedgehog pathway inhibitors regardless of PTCH1 status.” See p. 10, penultimate paragraph.
The status, success or failure, of a clinical trial or is not the standard for obviousness. While commercial success is one of multiple factors considered in the obviousness analysis, the status of a potential merger or acquisition is not considered in the obviousness analysis.
Nonetheless, Epstein discloses where 2% patidegib gel shrank surgically-eligible BCCs (SEBs) compared with vehicle (P = 0.04); 2% and 4% gels caused tumor CR in 25% of existing SEBs (P = 0.02). Epstein goes on to state where “topical patidegib gel has the potential to prevent and mitigate facial BCCs in Gorlin patients.”
Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980). See MPEP 716.02 (d) and MPEP 716.02 (e).
The present claims include the phrase “comprising” in line 2 of claim 1 and line 2 of claim 10. The transitional term "comprising", which is synonymous with "including," "containing," or "characterized by," is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. See, e.g., Mars Inc. v. H.J. Heinz Co., 377 F.3d 1369, 1376, 71 USPQ2d 1837, 1843 (Fed. Cir. 2004). See MPEP 2111.03.
Applicant refers to alleged unexpected results; however, even if the results were considered unexpected, the results would not be commensurate in scope with the scope claims. As the present claims encompass the treatment and prevention of BCC lesions, caused in part by genetic mutation, it would be expected by one of ordinary skill in the art the entire population is susceptible to the claimed condition. The results provided do not occur over the entire claimed range (method of treatment and/or prevention of basal cell carcinoma (BCC) lesions in a patient suffering from Gorlin syndrome, comprising topically administering a pharmaceutical composition comprising any amount of patidegib and any pharmaceutically acceptable carrier, wherein the subject must have a confirmed has a genetic mutation PTCH1 mutation prior to the initiation of said therapy, said therapy occurring at any administration schedule) of present claim 1.
The fact the present claims encompass treatment as well as prevention means practicing the method of the prior art would entail administration to a patient population embraced by the instant claims, Gorlin syndrome subjects carrying the PTCH1 genetic mutation prior to the initiation of therapy.
Further as the prior art teaches the efficacy of other hedgehog inhibitors regardless of PTCH1-mutation status serves as further evidence for the lack of unexpected results for the success of another species of the disclosed genus having similarly reported efficacy.
As NCT ‘084 in combination with Epstein disclose a method of treatment and prevention of basal cell carcinoma lesions in patients having PTCH1 mutation and Gorlin syndrome comprising topically administering 2% and 4% patidegib gel, the instant claims are prima facie obvious. In view of the results summarized by Epstein, there would be a reasonable expectation of success for one of skill in the art to treat or prevent BCC lesions with topical administration of patidegib gel.
Therefore, the previous rejection is maintained in an amended form to address Applicant’s traversal.
Claim Rejections - 35 USC § 103
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 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.
Claims 1-2 and 6-14 are rejected under 35 U.S.C. 103 as being unpatentable over Clinical Trial NCT02762084 (PellePharm Inc, study closed 07/23/2020; references from V10 study update 07/08/2020; henceforth NCT ‘084), in view of Epstein (Epstein, Ervin H., et al. "Hedgehog pathway inhibition by topical patidegib to reduce BCC burden in patients with basal cell nevus (Gorlin) syndrome." (2018): e21626-e21626.).
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
NCT ‘084 discloses a multicenter, double-blind, randomized, vehicle-controlled study that evaluates the efficacy and safety of patidegib gel 2% and 4% in comparison with vehicle in participants having PTCH1 genetic mutation and suffering from Gorlin syndrome. See page 3 and 7 of NCT ‘084. See instant claims 1 and 7.
NCT ‘084 discloses patidegib will be applied topically to the entire face as well as to treatment-targeted surgically eligible basal cell carcinomas (SEBs) at other anatomical sites twice daily for 26 weeks of treatment. See Detailed Description in NCT ‘084 page 3. See instant claims 11 and 12.
NCT ‘084 discloses study inclusion criteria comprises participant must have a history of at least 10 BCCs prior to screening. See page 11 of NCT ‘084. See instant claims 2 and 6.
The Clinical Study Protocol of the NCT ‘084 trial also discloses where one of the major inclusion criteria for patients of the study is PTCH1 gene mutation in normal tissue. See page 8 of the Clinical Study Protocol attached herewith.
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Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
NCT ’084 does not disclose wherein the method of treatment basal cell carcinoma (BCC) lesions results in a reduction of BCC lesion size or resolved BCC lesion over time or wherein the method refers to preventing formation of new BCC lesions, or new surgically eligible BCC lesions. See instant claims 8-10.
NCT ‘084 does not disclose wherein the subject does not develop drug resistance or following a discontinuation period of administration during the treatment, the drug efficacy is not affected. See instant claims 13-14.
Finding of prima facie obviousness --- rationale and motivation (See
MPEP § 2142-2143)
Epstein discloses the following:
a modified ITT analysis, 2% gel shrank SEBs compared with vehicle (P = 0.04); 2% and 4% gels caused tumor CR in 25% of existing SEBs (P = 0.02). No vehicle-treated SEB disappeared. 3 of 5 (60%) patients applying vehicle gel developed a new facial SEB; 2 of 12 (16%) patients applying 2% or 4% gel developed a new facial SEB (p = 0.02 for prevention). Shrinkage of SEBs only occurred in those in whom HH pathway activity was reduced after 6 weeks of topical application. Importantly, unlike oral HH inhibitors, topical patidegib caused no hair loss, taste loss, or muscle cramps and produced circulating blood levels three orders of magnitude lower than those with oral patidegib. Conclusions: Topical patidegib gel has the potential to prevent and mitigate facial BCCs in Gorlin patients.
See Abstract of Epstein. See instant claims 8-10 and 13-14.
The present claims include the phrase “comprising” in line 2 of claim 1 and line 2 of claim 10. The transitional term "comprising", which is synonymous with "including," "containing," or "characterized by," is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. See, e.g., Mars Inc. v. H.J. Heinz Co., 377 F.3d 1369, 1376, 71 USPQ2d 1837, 1843 (Fed. Cir. 2004). See MPEP 2111.03. Further, the fact the claims encompass treatment as well as prevention means practicing the method of the prior art would entail administration to a patient population embraced by the instant claims, Gorlin syndrome subjects carrying the PTCH1 genetic mutation prior to the initiation of therapy. One of ordinary skill in the art would be expect the entire population is susceptible in some part to the presently claimed mutation and condition.
Conclusive proof of efficacy is not required to show a reasonable expectation of success. See MPEP 2143.02, Section I. OSI Pharm., LLC v. Apotex Inc., 939 F.3d 1375, 1385, 2019 USPQ2d 379681 (Fed. Cir. 2019) ("To be clear, we do not hold today that efficacy data is always required for a reasonable expectation of success. Nor are we requiring ‘absolute predictability of success.’"); Acorda Therapeutics, Inc. v. Roxane Lab., Inc., 903 F.3d 1310, 1333, 128 USPQ2d 1001, 1018 (Fed. Cir. 2018) ("This court has long rejected a requirement of ‘[c]onclusive proof of efficacy’ for obviousness." (citing to Hoffmann-La Roche Inc. v. Apotex Inc., 748 F.3d 1326, 1331 (Fed. Cir. 2014); PharmaStem Therapeutics, Inc. v. ViaCell, Inc., 491 F.3d 1342, 1364 (Fed. Cir. 2007); Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1364, 1367–68 (Fed. Cir. 2007) (reasoning that "the expectation of success need only be reasonable, not absolute")).
The prior art need not teach, suggest or disclose where the method of treatment and/or prevention of BCC lesion is 100% effective in patients with Gorlin PTCH1 mutation.
A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989). See also Upsher-Smith Labs. v. Pamlab, LLC, 412 F.3d 1319, 1323, 75 USPQ2d 1213, 1215 (Fed. Cir. 2005).
NCT’ 084 requires where “subject must meet diagnostic criteria for basal cell nevus syndrome (BCNS) including major criterion #3a plus one additional major criterion” and further lists “PTCH1 gene mutation in normal tissue” as a major criterion, would motivate one of skill in the art to at least assess whether subjects meet the criterion.
Epstein discloses where 2% patidegib gel shrank surgically-eligible BCCs (SEBs) compared with vehicle (P = 0.04); 2% and 4% gels caused tumor CR in 25% of existing SEBs (P = 0.02). Epstein goes on to state where “topical patidegib gel has the potential to prevent and mitigate facial BCCs in Gorlin patients.”
The NCT ‘084 reference does not teach away from a method of treatment of Gorlin syndrome patients having the PTCH1 mutation at the time of therapy. As the claims encompass the treatment and prevention of BCC lesions, caused in part by genetic mutation, it would be expected by one of ordinary skill in the art the entire population is susceptible to the claimed condition. In view of the results summarized by Epstein, there would be a reasonable expectation of success for one of skill in the art to treat or prevent BCC lesions with topical administration of patidegib gel.
The present claims do not exclude an embodiment of a method of treatment and/or prevention of basal cell carcinoma (BCC) lesions in a patient suffering from Gorlin syndrome where one of ordinary skill in the art performs a general screening of all participants for mutations and subsequently treats each participant with 2% or 4% patidegib gel, regardless of mutation status.
As NCT ‘084 in combination with Epstein disclose a method of treatment and prevention of basal cell carcinoma lesions in patients having PTCH1 mutation and Gorlin syndrome comprising topically administering 2% and 4% patidegib gel, the instant claims are prima facie obvious.
Conclusion
Claims 1-2 and 6-14 are rejected.
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.
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/QUINCY A. MCKOY/
Patent Examiner
Art Unit 1626
/KAMAL A SAEED/Primary Examiner, Art Unit 1626