www.uspto.gov
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`UNITED STATES DEPARTMENT OF COMMERCE
`United States Patent and Trademark Office
`Address: COMMISSIONER FOR PATENTS
`PO. Box 1450
`Alexandria, Virginia 2231371450
`
`16/075,828
`
`08/06/2018
`
`Daiki MURASE
`
`2537.1600002/MAC
`
`1355
`
`STERNE, KESSLER, GOLDSTEIN & FOX P.L.L.C.
`1100 NEW YORK AVENUE, N.W.
`WASHINGTON, DC 20005
`
`KOSTURKO. GEORGE W
`
`ART UNIT
`
`1628
`
`PAPER NUMBER
`
`NOTIFICATION DATE
`
`DELIVERY MODE
`
`02/06/2020
`
`ELECTRONIC
`
`Please find below and/or attached an Office communication concerning this application or proceeding.
`
`The time period for reply, if any, is set in the attached communication.
`
`Notice of the Office communication was sent electronically on above—indicated "Notification Date" to the
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`following e—mail address(es):
`e-offiee @ sternekessler. com
`
`PTOL-90A (Rev. 04/07)
`
`

`

`017/09 A0170” Summary
`
`Application No.
`16/075,828
`Examiner
`GEORGE w KOSTURKO
`
`Applicant(s)
`MU RASE et al.
`Art Unit
`AIA (FITF) Status
`1628
`Yes
`
`- The MAILING DA TE of this communication appears on the cover sheet wit/7 the correspondence address -
`Period for Reply
`
`A SHORTENED STATUTORY PERIOD FOR REPLY IS SET TO EXPIRE g MONTHS FROM THE MAILING
`DATE OF THIS COMMUNICATION.
`Extensions of time may be available under the provisions of 37 CFR 1.136(a). In no event, however, may a reply be timely filed after SIX (6) MONTHS from the mailing
`date of this communication.
`|f NO period for reply is specified above, the maximum statutory period will apply and will expire SIX (6) MONTHS from the mailing date of this communication.
`-
`- Failure to reply within the set or extended period for reply will, by statute, cause the application to become ABANDONED (35 U.S.C. § 133).
`Any reply received by the Office later than three months after the mailing date of this communication, even if timely filed, may reduce any earned patent term
`adjustment. See 37 CFR 1.704(b).
`
`Status
`
`1)I Responsive to communication(s) filed on 11/13/2019.
`CI A declaration(s)/affidavit(s) under 37 CFR 1.130(b) was/were filed on
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`2a)I This action is FINAL.
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`2b) D This action is non-final.
`
`3)[:] An election was made by the applicant in response to a restriction requirement set forth during the interview
`on
`; the restriction requirement and election have been incorporated into this action.
`
`4):] Since this application is in condition for allowance except for formal matters, prosecution as to the merits is
`closed in accordance with the practice under Expade Quay/e, 1935 CD. 11, 453 O.G. 213.
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`Disposition of Claims*
`
`5)
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`Claim(s) fl is/are pending in the application.
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`5a) Of the above Claim(s) 1—11,13—15 and 17—19 is/are withdrawn from consideration.
`
`
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`E] Claim(ss)_is/are allowed.
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`Claim(ss) 12,16 and 20 is/are rejected.
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`1:] Claim(ss_) is/are objected to.
`
`) ) ) )
`
`S)
`are subject to restriction and/or election requirement
`C] Claim(s
`* If any claims have been determined allowable, you may be eligible to benefit from the Patent Prosecution Highway program at a
`
`participating intellectual property office for the corresponding application. For more information, please see
`
`http://www.jjgptgng/patents/init_event§/pph/index.'§p or send an inquiry to PPeredhack@gsptg.ggv.
`
`Application Papers
`
`10):] The specification is objected to by the Examiner.
`
`11)I The drawing(s) filed on 08/06/2018 is/are: a)I accepted or b)D objected to by the Examiner.
`Applicant may not request that any objection to the drawing(s) be held in abeyance. See 37 CFR 1.85(a).
`Replacement drawing sheet(s) including the correction is required if the drawing(s) is objected to. See 37 CFR 1.121 (d).
`
`Priority under 35 U.S.C. § 119
`
`12)I Acknowledgment is made of a claim for foreign priority under 35 U.S.C. § 119(a)-(d) or (f).
`Certified copies:
`
`a). All
`
`b)C] Some**
`
`c)[j None of the:
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`1.I Certified copies of the priority documents have been received.
`
`2E] Certified copies of the priority documents have been received in Application No.
`
`3C] Copies of the certified copies of the priority documents have been received in this National Stage
`application from the International Bureau (PCT Rule 17.2(a)).
`
`** See the attached detailed Office action for a list of the certified copies not received.
`
`Attachment(s)
`
`1)
`
`Notice of References Cited (PTO-892)
`
`Information Disclosure Statement(s) (PTO/SB/08a and/or PTO/SB/08b)
`2)
`Paper No(s)/Mail Date_
`U.S. Patent and Trademark Office
`
`3) E] Interview Summary (PTO-413)
`Paper No(s)/Mail Date
`4) CI Other-
`
`PTOL-326 (Rev. 11-13)
`
`Office Action Summary
`
`Part of Paper No./Mai| Date 20200128
`
`

`

`Application/Control Number: 16/075,828
`Art Unit: 1628
`
`Page 2
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`DETAILED ACTION
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`Notice of Pre-AIA or AIA Status
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`1.
`
`The present application, filed on or after March 16, 2013, is being examined
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`under the first inventor to file provisions of the AIA. Claims 1-21 are currently pending.
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`Information Disclosure Statement
`
`2.
`
`The information disclosure statement (IDS) submitted on 11/13/2019 is in
`
`compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure
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`statement is being considered by the examiner.
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`3.
`
`Status of Claims
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`4.
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`As indicated in the Office Action of 06/25/2019, claims 1-11, 13-15, 17-19 and
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`21 were withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being
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`drawn to a nonelected invention, there being no allowable generic or linking claim.
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`Election was made with traverse in the reply filed on 05/29/2019. Claims 12, 16 and 20
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`are the subject matter of this Office Action.
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`5.
`
`Response to Amendment
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`6.
`
`Applicant’s amendments, filed 11/13/2019 are acknowledged. Applicant has
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`amended claim 12 as follows: A method for darkening a subiect’s skin or hair color,
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`comprising externally applying, to a site on the subiect’s skin or hair at which the subiect
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`desires to darken the subiect’s skin or hair color, an effective amount of an external
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`preparation that comprises administratmg-te-ephegesting—in—a—subjeet—m—need—Heereefrat
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`least one compound selected from the group consisting of a berberine or a salt thereof,
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`proguanil or a salt thereof and phenformin or a salt thereof in—an—effeetive—ameunt fl
`
`

`

`Application/Control Number: 16/075,828
`Art Unit: 1628
`
`Page 3
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`darkening the subject’s skin or hair color at the site as a result of the applying. Claims
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`16 and 20 have also been amended.
`
`7.
`
`In response to Applicant’s amendments, the corresponding 35 USC 112
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`paragraph B and D rejections of record have been withdrawn. The examiner has
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`interpreted that the claimed subject who “desires to darken the subject’s skin or hair
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`color” to not read on patients whom administered the elected antimalarial proguanil and
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`developed blotchy skin pigmentation as a result of phototoxicity. Therefore, the
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`corresponding 35 USC 102(a) rejections of record have been withdrawn. In addition, the
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`corresponding 35 USC 103 (a) rejection of record in view of FR2901133 has been
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`withdrawn. While FR2901133 teaches proguanil as a specie of glycolysis activator and
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`is used to reduce “skin fading” (page 32-36), there is no teaching nor suggestion within
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`FR2901133 that administration of said proguanil to reduce “skin fading” would
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`effectively darken the subject’s skin upon application.
`
`8.
`
`9.
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`Species Election
`
`10.
`
`Applicant’s election of proguanil in the reply filed on 05/29/2019. In view of
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`Applicant’s amendments to claims 12, 16 and 20, and a careful review of the prior art,
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`the elected specie proguanil is free of the prior art. Claim 12, wherein the external
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`preparation comprises proguanil would be allowable if written in independent format.
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`The examiner has expanded the genus of species listed in claim 12 to alternatives of
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`the Markush group, such as berberine and the corresponding rejections are based on
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`the specie expansion.
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`

`

`Application/Control Number: 16/075,828
`Art Unit: 1628
`
`Page 4
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`11.
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`Applicant's arguments, filed 11/13/2019 have been fully considered. Rejections
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`and/or objections not reiterated from the previous Office Action are hereby withdrawn.
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`The following rejections and/or objections are either reiterated or newly applied. They
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`constitute the complete set of rejections and objections presently being applied to the
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`instant application.
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`12.
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`Claim Rejections - 35 USC § 102
`
`13.
`
`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
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`correction of the statutory basis for the rejection will not be considered a new ground of
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`rejection if the prior art relied upon, and the rationale supporting the rejection, would be
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`the same under either status.
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`14.
`
`The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that
`
`form the basis for the rejections under this section made in this Office action:
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`A person shall be entitled to a patent unless —
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`(a)(1) the claimed invention was patented, described in a printed publication, or in public use,
`on sale or othenNise available to the public before the effective filing date of the claimed
`invention.
`
`15.
`
`Claim(s) 12, 16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by
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`Kuniharu et al (JP05-078222 published 03/30/1993; machine translation provided in the
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`IDS of 08/29/2018).
`
`16.
`
`Kuniharu teaches method of preventing gray hair in a subject comprising topically
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`administering a cosmetic composition comprising 0.01 -10% wt. berberine (abstract,
`
`[0006], [0010], [0012], [0027]-[0029], Table 2). Topical external cosmetic formulations
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`

`

`Application/Control Number: 16/075,828
`Art Unit: 1628
`
`Page 5
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`are embodied in the teachings of Kuniharu, including creams, lotions and emulsions
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`(abstract, [0011]). Kuniharu teaches that berberine exhibits a melanogenesis promoting
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`action by blocking the formation of canities in the administered subject’s hair, which lead
`
`to the development of loss of melanin in the hair ([0002], [0006], [0017], [0026]-[0029]
`
`Table 2). As shown in Table 2, after 6 months, the amount of canities are reduced in the
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`treated hair, resulting in a reduction of gray/white in the hair thereby darkening of the
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`hair compared to control.
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`17.
`
`Regarding the limitation of claim 16, Kuniharu teaches preparation of a 1% wt.
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`berberine solution (10 g per 1000 mL), wherein 1.5 mL of said 1% wt. berberine solution
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`was applied to the hair of male and female adults in need of inhibiting the formation of
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`canities ([0026-0029], Table 2). Each 1.5 mL of said 1% wt. berberine solution
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`corresponds to a mass of 0.015g berberine. Application of 0.015 g berberine to said
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`adult in need of inhibiting the formation of canities corresponds to the administration of
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`15 mg per day to said adult, which lies inside the therapeutic range of claim 16.
`
`18.
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`Claim Rejections - 35 USC § 103
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`19.
`
`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
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`correction of the statutory basis 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.
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`

`

`Application/Control Number: 16/075,828
`Art Unit: 1628
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`Page 6
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`20.
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`The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148
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`USPQ 459 (1966), that are applied for establishing a background for determining
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`obviousness under 35 U.S.C. 103 are summarized as follows:
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`1. Determining the scope and contents of the prior art.
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`2. Ascertaining the differences between the prior art and the claims at issue.
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`3. Resolving the level of ordinary skill in the pertinent art.
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`4. Considering objective evidence present in the application indicating
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`obviousness or nonobviousness.
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`21.
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`Claims 12, 16 and 20 are rejected under 35 U.S.C. 103 as being unpatentable
`
`over Kuniharu et al (JP05-078222 published 03/30/1993; machine translation provided
`
`in the IDS of 08/29/2018).
`
`22.
`
`As discussed above, Kuniharu teaches method of preventing gray hair in a
`
`subject comprising topically administering a cosmetic composition comprising 0.01 -1 0%
`
`wt. berberine (abstract, [0006], [0010], [0012], [0027]-[0029], Table 2). Topical external
`
`cosmetic formulations are embodied in the teachings of Kuniharu, including creams,
`
`lotions and emulsions (abstract, [0011]). Kuniharu teaches that berberine exhibits a
`
`melanogenesis promoting action by blocking the formation of canities in the
`
`administered subject’s hair, which lead to the development of loss of melanin in the hair
`
`([0002], [0006], [0017], [0026]-[0029] Table 2). As shown in Table 2, after 6 months, the
`
`amount of canities are reduced in the treated hair, resulting in a reduction of gray/white
`
`in the hair or darkening of the hair compared to control.
`
`23.
`
`Regarding the limitation of claim 16, Kuniharu teaches preparation of a 1% wt.
`
`berberine solution (10 g per 1000 mL), wherein 1.5 mL of said 1% wt. berberine solution
`
`

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`Application/Control Number: 16/075,828
`Art Unit: 1628
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`Page 7
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`was applied to the hair of male and female adults in need of inhibiting the formation of
`
`canities ([0026-0029], Table 2). Each 1.5 mL of said 1% wt. berberine solution
`
`corresponds to a mass of 0.015g berberine. Application of 0.015 g berberine to said
`
`adult in need of inhibiting the formation of canities corresponds to the administration of
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`15 mg per day to said adult, which lies inside the therapeutic range of claim 16.
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`24.
`
`Kuniharu does not explicitly teach the administration of said berberine cosmetic
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`composition in a dose of 0.01-10 mg per 100cm2 per time (claim 20).
`
`25.
`
`It is noted that an area of 100 cm2 corresponds to 0.01 m2. Thus, the therapeutic
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`range of claim 20 corresponds to a ratio of 1 mg/m2 to 1000 mg/m2 per period of time.
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`As discussed above, Kuniharu exemplifies administration of 15 mg per 1.5 mL applied
`
`to the hair of male and female adults in need of inhibiting the formation of canities,
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`thereby darkening the hair of the administered subject compared to control ([0026-
`
`0029], Table 2). As evidenced by Reagan-Shaw et al., (FASEBJ Vol. 22 pages 659-661,
`
`Published 2007, Table 1), conversion of mg/kg to mg/m2 in an adult 60 kg human is to
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`multiply the mg/kg dose by the Km factor of 1.6 (table 1). Administration of 15 mg per 60
`
`kg adult yields a dose of 0.25 mg/kg. Multiplying the 0.25 mg/kg dose by the Km factor
`
`of 1.6 corresponds to a dose of 0.4 mg/m2 for said 1% wt. berberine composition.
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`26.
`
`It is also noted that Kuniharu teaches that the dose of the gray hair inhibiting
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`berberine can be adjusted to include 10% wt. of the composition ([0012]). A 1.5 mL
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`solution of said 10% wt. berberine solution applied to the hair of male and female adults
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`in need of inhibiting the formation of canities would result in a dose of 4 mg/m2 in view
`
`of the calculations above, which lies within the therapeutic window of 1 mg/m2 to 1000
`
`mg/m2 per period of time in claim 20. Applicant is reminded of MPEP 2144.05 wherein
`
`

`

`Application/Control Number: 16/075,828
`Art Unit: 1628
`
`Page 8
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`in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior
`
`art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ
`
`90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990)
`
`(The prior art taught carbon monoxide concentrations of "about 1-5%" while the claim
`
`was limited to "more than 5%." The court held that "about 1-5%" allowed for
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`concentrations slightly above 5% thus the ranges overlapped.);
`
`27.
`
`Therefore, prior to the time of the instant invention. one at erdinary skiii in the art
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`wouici have feund it prima facie obvieus to administer the grey hair inhibiting berberine
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`hair tonic of Kuniharu in a cericei‘itration of 0.01—10 mg per 10mm? in order to effectiveiy
`
`inhibit melanin decomposition in the hair. Motivation to administer a dose of 0.01 -10 mg
`
`per 100 cm2, or 1 mg/m2 to 1000 mg/m2 (based on a conversion of 100 cm2 corresponds
`
`to 0.01 m2) logically flows from the fact that a dose of 4 mg/m2 of berberine was taught
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`as suitable dose of berberine to be effective at inhibiting the formation of canities in the
`
`hair of treated subject (abstract, [0012], [0026-002], Table 2). As discussed above, said
`
`10% wt. berberine composition corresponds to a dose of 4 mg/m2 based on
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`administration of 1.5 mL of said 10% wt. berberine composition to the hair of a 60 kg
`
`subject. Said 1.5 mL is a volume embodied in the working examples of Kuniharu
`
`([0026]-[0028], Table 2). Motivation to select a dose of 4 mg/m2 berberine naturally
`
`flows from the fact that it is well settled that it is a matter of obviousness for one of
`
`ordinary skill in the art to select a particular component from among many disclosed by
`
`the prior art as long as it is taught that the selection will result in the disclosed effect,
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`even when the possible selections number 1200 or in the thousands. Merck & Co., Inc.
`
`V. Biocraff Labs., Inc., 874 F.2d 804, 807 (Fed. Cir. 1989); In re Cor/(ill, 771 F.2d 1496,
`
`

`

`Application/Control Number: 16/075,828
`Art Unit: 1628
`
`Page 9
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`1500 (Fed. Cir. 1985).” In the instant case, as a dose of 4 mg/m2 berberine was taught
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`by Kuniharu to be a suitable dose of berberine in order to be effective at inhibiting gray
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`hair in the administered subject, a skilled artisan would have predicted with a
`
`reasonable expectation of success, that topical administration of said dose of berberine
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`would have effectively inhibited the formation of gray hair in the treated subject, thereby
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`darkening the hair of said subject.
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`28.
`
`29.
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`Conclusion
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`30.
`
`Applicant's amendment necessitated the new ground(s) of rejection presented in
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`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
`
`CFR1.136(a).
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`A shortened statutory period for reply to this final action is set to expire THREE
`
`MONTHS from the mailing date of this action.
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`In the event a first reply is filed within
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`TWO MONTHS of the mailing date of this final action and the advisory action is not
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`mailed until after the end of the THREE-MONTH shortened statutory period, then the
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`shortened statutory period will expire on the date the advisory action is mailed, and any
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`extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of
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`the advisory action.
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`In no event, however, will the statutory period for reply expire later
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`than SIX MONTHS from the date of this final action.
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`

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`Application/Control Number: 16/075,828
`Art Unit: 1628
`
`Page 10
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`31.
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`Any inquiry concerning this communication or earlier communications from the
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`examiner should be directed to GEORGE W KOSTURKO whose telephone number is
`
`(571)270-5903. The examiner can normally be reached on M-F 9:00-5:30.
`
`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, Winston Shen can be reached on 571-272—3157. The fax phone number for
`
`the organization where this application or proceeding is assigned is 571-273-8300.
`
`Information regarding the status of an application may be obtained from the
`
`Patent Application Information Retrieval (PAIR) system. Status information for
`
`published applications may be obtained from either Private PAIR or Public PAIR.
`
`Status information for unpublished applications is available through Private PAIR only.
`
`For more information about the PAIR system, see https://ppair-
`
`my.uspto.gov/pair/PrivatePair. Should you have questions on access to the Private
`
`PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
`
`If you would like assistance from a USPTO Customer Service Representative or access
`
`to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-
`
`272-1000.
`
`/TIMOTHY P THOMAS/
`
`GEORGE W. KOSTURKO
`
`Primary Examiner, Art Unit 1611
`
`Examiner
`Art Unit 1628
`
`