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 and Election
Claims 1, 3, 4, 9-11, 22-26, and 28-34 are pending. Claims 1, 9, and 22 have been amended.
Examination on the merits commences on claims 1, 3, 4, 9-11, 22-26, and 28-34.
Applicants are informed that the rejections and/or objections of the previous Office action not stated below have been withdrawn from consideration in view of the Applicant' s arguments and/or amendments. Applicant’s amendments and arguments have been thoroughly reviewed but are not persuasive to place the claims in condition for allowance for the reasons that follow.
Claim Rejections - 35 USC § 103 - SUSTAINED
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.
Claim(s) 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over
Claim(s) 1, 3, and 4 is/are rejected under 35 U.S.C. 103 as being unpatentable over Peuker (Peuker, H., EP-1759700-A1, 2007) in view of Liu (Liu, L., CN 108795842 A, published 11/13/2018) and Chapman (Chapman, Sandra, et al. "The effect of Rho kinase inhibition on long-term keratinocyte proliferation is rapid and conditional." Stem cell research & therapy 5.2 (2014): 60.) and Shaw (Shaw, Peter X., et al. "Topical administration of a Rock/Net inhibitor promotes retinal ganglion cell survival and axon regeneration after optic nerve injury." Experimental eye research 158 (2017): 33-42.).
Regarding claim 1, Peuker teaches topical application of small molecule inhibitors to treat hypopigmentation disorders [0001] such as vitiligo [0003]. Peuker teaches mechanisms for disease destruction of melanocytes are caused from a composite of several normal processes influencing melanocyte function, proliferation and/or survival [0002]. Peuker teaches application of combinations of small molecule inhibitors and adjuvant active agents in the pro-pigmentation skin therapeutic method [0106].
Peuker does not teach the small molecule inhibitor as a Rock1 inhibitor.
Liu teaches preparation of melanocytes using the growth activating Rock1 small molecule inhibitor Y27632 then administering those melanocytes to the skin of subjects with the skin de-pigmentation disorder vitiligo (claim 9 and 10 and (pg 4 para 5). Liu teaches the melanocytes prepared by the invention are transplanted onto the skin of the subject (pg 4 para 5).
Chapman teaches ROCK inhibition rapidly and conditionally induces indefinite proliferation of keratinocytes in a method that has far-reaching applications for basic research, as well as for regenerative and personalized medicine (abstract). Chapman teaches keratinocytes cultured with small molecule ROCK inhibitors such as Y-27632 show that the effect of ROCK inhibition on cellular proliferation is immediate and ROCK inhibited cells proliferate rapidly and without differentiation or stratification and efficiently enhance the survival lifespan of keratinocytes (abstract).
Shaw teaches Rock1 inhibitors such as AR-13324 (Netarsudil, Rhopressa) as an effective topical agent (2.2) which promotes cellular growth (pg 34 para 3).
It would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have modified Peuker’s method of topical combination small molecule inhibitor treatment of vitiligo, which causes skin pigmented cell death, to also include a ROCK1 inhibitor so as to enhance pigmented cell survival and proliferation. It would have merely amounted to a simple combination of prior art elements according to known methods to yield predictable results. The skilled artisan would have had a reasonable expectation that Liu’s ROCK1 inhibitor could be effectively applied topically because Shaw teaches Rock1 inhibitors as effective topical agents. It would have been predictable that Rock1 inhibitors added to Peuker’s vitiligo treatment would be effective at treating subjects with vitiligo because Peuker teaches vitiligo as a disease caused by melanocyte/keratinocyte destruction and Chapman and Shaw teach Rock1 inhibitors promote cell survival. The skilled artisan would be motivated to employ Liu’s Y27632 ROCK1 inhibitor in Peuker’s topical application in order to expand survival of pigmentation cells on the skin of subjects suffering from the hypopigmentation disorder vitiligo.
Regarding claims 3 and 4, Liu teaches preparation of melanocytes using the growth activating Rock1 small molecule inhibitor Y27632 then administering those melanocytes to the skin of subjects with the skin de-pigmentation disorder vitiligo (claim 9 and 10 and (pg 4 para 5).
Claim(s) 9-11, 22-26, and 28-34 is/are rejected under 35 U.S.C. 103 as being unpatentable over Peuker (Peuker, H., EP-1759700-A1, 2007) in view of Liu (Liu, L., CN 108795842 A, published 11/13/2018) and Chapman (Chapman, Sandra, et al. "The effect of Rho kinase inhibition on long-term keratinocyte proliferation is rapid and conditional." Stem cell research & therapy 5.2 (2014): 60.) and Shaw (Shaw, Peter X., et al. "Topical administration of a Rock/Net inhibitor promotes retinal ganglion cell survival and axon regeneration after optic nerve injury." Experimental eye research 158 (2017): 33-42.) as applied above to claim 1, in further view of Mujahid of record (Mujahid, Nisma, et al. Cell reports 19.11 (2017): 2177-2184.), claims 31 and 32 as evidenced by Lin (Lin, Cheng-Wen, et al. "Discovery and preclinical development of netarsudil, a novel ocular hypotensive agent for the treatment of glaucoma." Journal of Ocular Pharmacology and Therapeutics 34.1-2 (2018): 40-51.).
The teachings of Peuker, Liu, Chapman, and Shaw as applied above for claim 1 are incorporated here.
Regarding claims 9-11, Peuker does not teach the combination therapy of ROCK1 small molecule inhibitors applied topically to treat vitiligo which also includes a small molecule SIK inhibitor.
Mujahid teaches a safe, viable method of topical pigment production through localized delivery to skin of topical SIK inhibitors applied for localized SIK inhibition (pg 2182 col 1 para 3). Mujahid teaches administering an inhibitor of salt induced kinase (SIK), optimized in composition for human skin penetration, to stimulate melanocytic pigment synthesis and induce skin darkening in a topical application for pigment and skin disorders (pg 2177 para 2). Mujahid teaches the second-generation SIK inhibitors, YKL 06-061 and YKL 06-062, induce darkening pigmentation as measured by reflective colorimetry analysis after topical treatment of human breast skin explants (Figure S3B and pg 2180 para 1).
It would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have modified Peuker’s modified method of topical combination small molecule inhibitor treatment of vitiligo, which causes skin pigmented cell death, to include along with a ROCK1 inhibitor such as Y-27632 (as deemed obvious in the rejection above) to also include Mujahid’s YKL 06-061 SIK inhibitor so as to enhance pigmentation and pigmented cell survival and proliferation. It would have merely amounted to a simple combination of prior art elements according to known methods to yield predictable results. The skilled artisan would have had a reasonable expectation that Mujahid’s YKL 06-061 SIK inhibitor could be effectively applied topically because Mujahid teaches effective topical application of SIK inhibitors. It would have been predictable that Mujahid’s YKL 06-061 SIK inhibitor added to Peuker’s modified vitiligo treatment including Rock1 inhibitors would be effective at treating subjects with vitiligo because Peuker teaches vitiligo as a disease caused by pigmented keratinocyte destruction, Mujahid teaches the YKL-06-061 SIK inhibitor increases skin pigmentation and Chapman and Shaw teach Rock1 inhibitors promote cell survival which would promote the survival and proliferation of those cells with enhanced pigmentation. The skilled artisan would be motivated to employ SIK inhibitors in Peuker’s modified topical application in order to expand pigmentation in cells and enhance survival of pigmented cells on the skin of subjects suffering from the hypopigmentation disorder vitiligo.
Regarding claims 22, 29, 30, 33, and 34, Mujahid (pg 2177 para 2, Figure S3B and pg 2180 para 1) and Liu (pg 4 para 5) teach SIK inhibitors YKL 06-061 and YKL 06-062, and the ROCK small molecule inhibitor Y27632, respectively, for topical application.
Regarding claims 23 and 24, Liu teaches growth activating Rock1 small molecule inhibitor Y27632 then administering those melanocytes to the skin of subjects with the skin de-pigmentation disorder vitiligo (claim 9 and 10 and (pg 4 para 5).
Regarding claims 25 and 26, Mujahid teaches the second-generation small molecule SIK inhibitors, YKL 06-061 and YKL 06-062, induce darkening pigmentation as measured by reflective colorimetry analysis after topical treatment of human breast skin explants (Figure S3B and pg 2180 para 1).
Regarding claim 28, Peuker teaches the medicament according to the present invention is prepared in a form suitable for topical use, preferably in form of an ointment, a gel, a plaster, an emulsion, a lotion, a foam, a cream, a cream of a mixed phase or amphiphilic emulsion system (oil/water-water/oil mixed phase), a liposome, a transfersome, a paste or a powder, or a solution or suspension [0059].
Regarding claims 31 and 32, Shaw teaches Rock1 inhibitors such as AR-13324 as an effective topical agent (2.2) which promotes cellular growth (pg 34 para 3), as evidenced by Lin who teaches netarsudil is also known as AR-13324 (pg 41 para 4).
Response to Arguments
Applicant’s arguments in the Remarks (Page 6) filed 5/22/26 are directed to the withdrawn §112 rejection. Amendments to the independent claims to limit the ROCK1 and SIK inhibitor to an oligonucleotide RNAi or small molecule inhibitor is sufficient to overcome the §112 Written Description rejection of record. Applicant further argues (Remarks Page 7-12) that the references of record, i.e. Peuker, Liu, Chapman, and Shaw, taken alone or in combination, neither teach nor suggest the claimed method of treatment and that a person of ordinary skill in the art would not have found motivation to modify their teachings to arrive at the claimed subject matter nor would have had a reasonable expectation of success in doing so. Applicant further argues that the Examiner's combination depends on impermissible hindsight reconstruction drawn from Applicant's own specification. Applicant’s arguments have been thoroughly reviewed and found unpersuasive for the reasons that follow.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Examiner notes that MPEP 2144 teaches that the references do not have to explicitly suggest to combine the teachings. Rather, establishing a prima facie case of obviousness requires a clear articulation of a rationale for combining the teachings of the references, and such rationale has been provided in the rejection above. In response to applicant's argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). Additionally, MPEP 2143.01 states, “Obviousness can be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so. In re Kahn, 441 F.3d 977, 986, 78 USPQ2d 1329, 1335 (Fed. Cir. 2006) (discussing rationale underlying the motivation-suggestion-teaching test as a guard against using hindsight in an obviousness analysis). A "motivation to combine may be found explicitly or implicitly in market forces; design incentives; the ‘interrelated teachings of multiple patents’; ‘any need or problem known in the field of endeavor at the time of invention and addressed by the patent’; and the background knowledge, creativity, and common sense of the person of ordinary skill." Zup v. Nash Mfg., 896 F.3d 1365, 1371, 127 USPQ2d 1423, 1427 (Fed. Cir. 2018) (quoting Plantronics, Inc. v. Aliph, Inc., 724 F.3d 1343, 1354 [107 USPQ2d 1706] (Fed. Cir. 2013) (citing Perfect Web Techs., Inc. v. InfoUSA, Inc., 587 F.3d 1324, 1328 [92 USPQ2d 1849] (Fed. Cir. 2009) (quoting KSR, 550 U.S. at 418-21)).”
In this case, Liu teaches preparation of melanocytes using the growth activating Rock1 small molecule inhibitor Y27632 then administering those melanocytes to the skin of subjects with the skin de-pigmentation disorder vitiligo (claim 9 and 10 and (pg 4 para 5). Liu teaches the melanocytes prepared by the invention are transplanted onto the skin of the subject (pg 4 para 5).
Shaw teaches Rock1 inhibitors such as AR-13324 (Netarsudil, Rhopressa) as an effective topical agent (2.2) which promotes cellular growth (pg 34 para 3).
As described in the §103 rejection above, it would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have modified Peuker’s method of topical combination small molecule inhibitor treatment of vitiligo, which causes skin pigmented cell death, to also include a ROCK1 inhibitor so as to enhance pigmented cell survival and proliferation. The skilled artisan would have had a reasonable expectation that Liu’s ROCK1 inhibitor could be effectively applied topically because Shaw teaches Rock1 inhibitors as effective topical agents. It would have been predictable that Rock1 inhibitors added to Peuker’s vitiligo treatment would be effective at treating subjects with vitiligo because Peuker teaches vitiligo as a disease caused by melanocyte/keratinocyte destruction and Chapman and Shaw teach Rock1 inhibitors promote cell survival. The skilled artisan would therefore be motivated to employ Liu’s Y27632 ROCK1 inhibitor in Peuker’s topical application in order to expand survival of pigmentation cells on the skin of subjects suffering from the hypopigmentation disorder vitiligo.
Regarding combining SIK inhibition specifically, as described above, Mujahid teaches a safe, viable method of topical pigment production through localized delivery to skin of topical SIK inhibitors applied for localized SIK inhibition (pg 2182 col 1 para 3). Mujahid teaches administering an inhibitor of salt induced kinase (SIK), optimized in composition for human skin penetration, to stimulate melanocytic pigment synthesis and induce skin darkening in a topical application for pigment and skin disorders (pg 2177 para 2). It would have been obvious to combine the SIK inhibition topically to Peuker’s modified ROCK1 inhibitor topical treatments of vitiligo for the reasons described in the §103 rejection above.
Conclusion
No claims are allowable.
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 extension fee 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 date of this final action.
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/JOHN CHARLES MCKILLOP/Examiner, Art Unit 1637
/EKATERINA POLIAKOVA-GEORGANTAS/Primary Examiner, Art Unit 1637
