INTERNATIONAL PATENT REVIEWS, LLC
`LON OCeAUAl
`
`US010357567B1
`
`2) United States Patent
`Lundanhlet al.
`
`cio) Patent No.
`(45) Date of Patent:
`
`US 10,357,567 B1
`dul. 23, 2019
`
`(56)
`
`(72)
`
`Filed:
`fon Ch
`(2006.01)
`AGIN 596
`(2006.01)
`AGIK 4100
`(2006.01)
`AGIP IND
`(2006.01)
`AGIK 90
`(2006.01)
`AGIK 31/75
`US. CL
`CPC. AGLK MI/M6L (2013.01), ALK 9/0014
`(20)3.01, AGIK 31/75 201301), AGIN $162
`(2013.01); ABEP 17/12 (2018.01 AGIN
`WOSAGS2 (2013.01); AGIN 2005/0659
`(2013.01):AGIN 2005/0663 (2013.01)
`Field ofClassification Search
`CPO veers AGIN $106; AGIN SA616; AGIN 5/062;
`AGIN 2050662; AGIN 200510663,
`AGIN 20051067;AGIK 41,0087, AGIK.
`41,0061, AGIK 41/0071; AGLK 41/0076;
`AGIK 31/74; A6IK 31/745; AGIK 31/75;
`AGIK 317%
`» DTNB, 89, 96, 100; 12R/89R
`USPC.
`Sevappleation file for complete searchhistory.
`
`IPR2022-00056
`
`References Cited
`(54) METHODS FOR PHOTODYNAMIC
`U.S. PATENT DOCUMENTS,
`=
`$0,262 A192. Kennady
`etal.
`(711) Applicant: DUSA Pharmaceuticals, Ine.
`SAMLS31 A
`81995. Zarate ot al
`S.21938 A
`S199 Kennedy aa
`Wilmington, MA (US)
`SAT4S28 A
`y
`Inventors: Seott Lundahl, Lexington, MA (US),
`SAD.279 A
`“
`.
`$505,726 A
`Michael Guitadaare, Corlise, MA
`S.72.895 A
`7/1998 Zarate ot al
`(US)
`C
`od)
`(73) Asegnee: DUSA Pharmaceuticals, Ine.
`FOREIGN PATENT DOCUMENTS
`Wilmington, MA (US)
`
`(*) Notee:—Subdjectto any disclaimer, the term ofthis=Wo WO.22:000003173 AT 122008
`
`puleat is extended or adjusiad under $8
`WO)
`WO.LTMO2M0 AL
`2017
`USC. 154(6) by 0 days,
`OTHER PUBLICATIONS
`15'869,164
`‘George J. Schneider Do etal... A Multicenter,Randomized,Vehiche-
`Jan, 12, 2018
`Comtrolted Phase 2 Study of Bue Light Photodynamic Thempy
`With Aripolevulinic Acié HC) 20% ‘Togucal Solution for the
`‘Treatment of Actinic Kerstoses on the Upper Extrenitios: The
`Fiffect ofOectusion Dering the Drug Iscubwion Period, Jownal of
`Drugs in Dermtology, vol 11, Issue 12, Dee, 2012, 10 pages
`(Continued)
`Primary Exarviner— Aimed M Farah
`(74) Attorney, Agent, or Firm — Foley & Lardner LLP
`(57)
`ABSTRACT
`4 raethod ofenhancing penetrationofa (opical composition
`of S.aminolenutinic acid (ALA)into tissue for photady-
`naraic therapy inclides topically epplying ALA to a treat-
`meal area to be Leated with photodysamic thenpy. The
`method further includes, after the AL
`pplied to the
`treatment area, covering the treatment area wih a lw
`density polyethylese barrier. The treatient area is covered
`with the low density polyethylene berrier prior to light
`treatment to minimize transepidernal water boss from the
`treatment area
`
`Initial Patent Review
`
`U.S. 10357567
`
`10 Claims, 12 Drawing Sheets
`
`Methods for Photodynamic Therapy
`
`Critical Date: January 12, 2018
`Expiration Date: January 12, 2038
`
`Biofrontera Exhibit 1036
`Biofrontera Inc. et al. v. DUSA Pharmaceuticals, Inc.
`
`1
`
`

`

`U.S. 10357567 Bi
`
`
`
`International Patent Reviews
`
`IPR Initial Review
`
`
`
`FC**
`RC*
`diel aleyy
`eel aia]
`URL
`
`https://patents.google.com/patent/US10357567|Jan 12 2018 Jani22038|55|99|
`*patent and non-patentliterature citations ** citing patents
`
`Patent Number
`
`10357567
`
`Methods for photodynamic therapy
`
`Description/ Application Area
`A method of enhancing penetration of a topical
`composition of 5-aminolevulinic acid (ALA) into
`tissue for photodynamic therapy is disclosed.
`The method includes topically applying ALA to a
`treatmentarea to be treated with
`photodynamic therapy. The method further
`includes, after the ALA is applied to the
`treatment area, covering the treatment area
`with a polymeric barrier ...
`
`
`
` Request for
`
`U.S. 10357567
`
`Date
`
`Action /Outcome
`
`
`Original Filing Jan 12 2018|Originally filed with claims 1-23.
`
`
`
`Apr 3 2018|I. Claims 1-8 and 16-23, drawn to alternative methods of enhancing
`Restriction/Election
`penetration of a topical composition into a tissue for photodynamic
`therapy, classified in A61 K41 /0061.
`
`This application contains claims directed a patentably distinct specie.
`Theinvention of Group I contains claims directed to the following
`patentably distinct species:
`
`Species A (claims directed to a method of enhancing penetration of a
`topical composition into tissue characterized by applying 5-
`aminolevulinic acid (molecular formula CSH9NQ3) to a bodytissue to
`be treated, see Par. 0007 and 0010ofthe specification), and
`
`Specie B (claims directed to method of enhancing penetration of a
`topical composition to a skin tissue characterized by applying 5-
`aminolevulinic acid hydrochloride (molecular formula: CSH10CINO3) to
`a body tissue to be treated,
`see Par. 0011).
`
`© 2021 INTERNATIONAL PATENT REVIEWS, LLC
`ALL RIGHTS RESERVED
`
`2
`
`

`

`Response to
`Request for
`Restriction/Election
`
`Apr 13 2018
`
`Non-Final Rejection
`
`Aug 9 2018
`
`Applicant
`Arguments
`
`Nov 2 1018
`
`II. Claims 9-15, drawn to a method of photodynamic treatment of a
`body/skin tissue, classified in A61 N 5/062.
`Applicant elected Group I, claims 1-8 and 16-23, without traverse and
`Species A, claims directed to a method of enhancing penetration of a
`topical composition into a tissue, characterized by applying 5-
`aminolevulinic acid (molecular formula C5H9N03), with traverse.
`
`
`Claims 9-15 and 21-23 withdrawn from consideration.
`
`Claims 1-8 and 16-20 rejected.
`
`Claims 1-8 and 16-20 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 pre-AIA the applicant regards as the
`invention.
`
`The term "low" in claim 1 line 5 and claim 16 line 6 is a relative term
`which renders the claim indefinite.
`
`Claim 8 recites the limitation "the maximum plasma" in line 1. There is
`insufficient antecedent basis for this limitation in the claim.
`
`Claims 1, 2, 5 and 16 rejected under 35 U.S.C. 102(a)(1) as being
`anticipated by Foguet Roca, Pub. No. U.S. 2009/0324727.
`
`Note: in the Background section of the instant application, the
`applicant describes the use of ALA compositions for photodynamic
`therapy as well known in the art. The applicant further indicates that
`the inventors found 'coving [sic] polyethylene for a period of time over
`a treatment area is effective to minimize trans-epidermal water loss
`from the treatment area’ (see Par. 006 of the specification). The
`examiner further notes that the use of surfactants such as polyethylene
`for coating on a surface to minimize water loss for a period of time, or
`on a surface of a medical capsule to minimize water absorption is well
`known in the art (see Pars. 0004 and 0208 of Parent et al., Pub. No.
`U.S. 2014/0010761; and Pars. 0090 and 0106 of Bonasera et al., Pub.
`No. U.S 2005/0090429).
`
`Claims 1 and 16 rejected under 35 U.S.C. 102(a)(1) as being
`anticipated by Trigiante, Pub. No. U.S. 2011 /0053965.
`
`
`Claim 1 amended to include allowable subject matter relating to claim
`4. Claims 2, 4, 9-15, 17, 18 and 21-233 were cancelled without
`prejudice or disclaimer. Claim 5 was rewritten into independent form
`and revised to include subject matter supported at least by paras.
`[0022], [0059], [0066] and [0073] of the specification as filed. New
`claims 24 and 25 include subject matter also supported by at least
`these portions of the disclosure. Claim 8 was amended for antecedent
`basis purposes. Claim 16 was amended to include allowable subject
`matter relating to claim 17. Claim 20 is amended for consistency with
`the amendments to claim 16.
`
`Claim 1 was amended by adding the phrase “removing the low density
`polyethylene barrier within 3 hours and then applying light to
`
`3
`
`

`

`Final Rejection
`
`Feb 25 2019
`
`
`Apr 12 2019
`
`
`Applicant Response
`
`
`Notice of Allowance
`
`
`Issue Notification
`
`
`Notice of
`Publication
`
`
`
`
`the treatment area.”
`
`Claim 16 was amended by adding the phrase “removing the low density
`polyethylene barrier so as to expose the treatment site; and
`illuminating the exposed treatment site with an illuminator so as to
`deliver a 10 J/cm2 dose of blue light.”
`
`Upon entry of the amendments, claims 1, 3, 5-8, 16, 19, 20, 24 and 25
`will be pending.
`
`Claims 1, 5-8, 16, 19, 20, 24 and 25 were allowed.
`
`Claim 3 was rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112,
`4th paragraph, as being of improper dependent form for failing to
`further limit the subject matter of the claim upon which it depends, or
`for failing to include all the limitations of the claim upon which it
`depends.
`
`
`Accepted cancellation of claim 3.
`
`
`Jun 3 2019
`
`
`The allowed claim(s) were 1,5-8, 16, 19-20 and 24-25.
`
`
`Jul 2 2019
`
`
`Issue date specified as Jul 23 2019 for US Patent 10357567
`
`
`Jul 18 2019
`
`
`US-2019-0216927-A 1 published on Jul 18 2019
`
`
`
`Litigation History
`
`U.S. Patent 10357567: none
`
`
`Current Orange Book Patent Data
`
`Active Ingredient: AMINOLEVULINIC ACID HYDROCHLORIDE
`Proprietary Name: LEVULAN
`Dosage Form; Route of Administration: SOLUTION; TOPICAL
`Strength: 20%
`Reference Listed Drug: Yes
`Reference Standard: Yes
`TE Code:
`Application Number: N020965
`Product Number: 001
`Approval Date: Dec 3, 1999
`Applicant Holder Full Name: DUSA PHARMACEUTICALS INC
`Marketing Status: Prescription
`
`
`
`4
`
`

`

`U.S. 10357567 Bi
`
`
`
`Product
`No
`
`Srltcald
`No
`
`Drug
`aecltcald
`Expiration Terao
`
`Drug
`Product
`
`BITE yA
`Requested
`
`Submission
`Date
`
`001
`
`10357567
`
`01/12/2038
`
`U-804
`
`08/02/2019
`
`Exclusivity Data
`
`Product No
`
`001
`
`Exclusivity Code
`
`Exclusivity Expiration
`
`1-766
`
`03/09/2021
`
`
`
`
`
`Relevant Patent or Publication
`
`Publication Date
`
`Dragieva, G., et al. "A randomized controlled clinical trial of topical photodynamic
`therapy with methyl aminolaevulinate in the treatment of actinic keratosesin
`transplant recipients." British Journal of Dermatology 151.1 (2004): 196-200.
`
`July 2004
`
`Kurwa, Habib A., et al. "A randomized paired comparison of photodynamic therapy
`and topical 5-fluorouracil in the treatment of actinic keratoses.” Journal of the
`American Academy of Dermatology 41.3 (1999): 414-418.
`
`September 1999
`
`Braathen, Lasse R., et al. "Guidelines on the use of photodynamic therapy for
`nonmelanomaskin cancer: an international consensus.” Journal of the American
`Academy of Dermatology 56.1 (2007): 125-143.
`
`January 2007
`
`MacCormack, Mollie A. "Photodynamic therapy in dermatology: an update on
`applications and outcomes." Seminars in cutaneous medicine and surgery. Vol. 27.
`No. 1. WB Saunders, 2008.
`
`March 2008
`
`Wolf, Peter, Edgar Rieger, and Helmut Kerl. "Topical photodynamic therapy with
`endogenousporphyrins after application of 5-aminolevulinic acid: an alternative
`treatment modality for solar keratoses, superficial squamouscell carcinomas, and
`basal cell carcinomas?" Journal of the American Academy of Dermatology 28.1
`(1993): 17-21.
`
`January 1993
`
`Ozog, David M., et al. "Photodynamic therapy:a clinical consensus guide."
`Dermatologic Surgery 42.7 (2016): 804-827.
`
`July 2016
`
`Schmieder, George J., Eugene Y. Huang, and Michael Jarratt. "A multicenter,
`randomized,vehicle-controlled phase 2 study of blue light photodynamic therapy
`with aminolevulinic acid HCl 20%topical solution for the treatment of actinic
`keratoses on the upper extremities: the effect of occlusion during the drug
`incubation period." Journal of drugs in dermatology: JDD 11.12 (2012): 1483-
`1489.*
`
`November 2012
`
`© 2021 INTERNATIONAL PATENT REVIEWS, LLC
`ALL RIGHTS RESERVED
`
`5
`
`

`

`U.S. 10357567 Bi
`
`
`
`WO 2009/003173 Ai to Sakamoto et a/.*
`
`FDA Label LEVULAN KERASTICK(aminolevulinic acid HCl) for Topical Solution,
`20%;Initial U.S. Approval: 1999
`
`*Cited during prosecution or on face of the patent.
`
`December 2008
`
`October 2006
`
`
`
`Ever-greening of the 5-ALA PDT Technology:
`
`The patentee originally filed an NDA (NDA 20-965) for “for LEVULAN® KERASTICK (aminolevulinic acid HCl) for
`Topical Solution, 20%, for use in photodynamic therapy with bluelight irradiation” on June 29, 1998 which was
`based at least on U.S. Patents 5,079,262 (issued 1992); 5,211,938 (issued 1993); 5,422,093 (issued 1995);
`5,954,703 (issued 1999); and 6,710,066 (issued 2004). The use of 5-ala in blue-light photodynamic therapy as
`Levulan® Kerastick was given FDA approval on December5, 1999.
`
`
`
`lea lam Olan ley
`
`Se l—6)
`
`2012-07-10
`
`Expiration (est)
`2038-01-12
`2018-05-01
`2018-05-01
`2019-06-17
`2018-05-01
`2016-03-23
`
`2017-10-31
`2012-06-06
`
`1993-05-18
`
`2013-09-30
`“— on original FDA Label 2006 as approved (NDA 20-965)
`
`U.S Patent 10357567 wasfiled as U.S. Appl. 15/869,164 on January 12, 2018. The expected expiration date of the
`‘567 is estimated to be January 12, 2038. This is a span of 46 years and 5 daysfrom the time of issuance of the
`first foundational patent. The ‘567 patent represents an abuse of the United States Patent system as an inequitable
`extension of valid patent rights by “ever-greening” the technology and should be invalidated as lacking novelty over
`the prior art cited below.
`
`The use of 5-aminolevullinic acid in photodynamic therapy using a 3-hour pretreatment under occlusion on the
`hands and forearms was very well known and developed at the time of the invention (January 12, 2018). Reviews
`have been published (see e.g., at least MacCormack and Ozog).
`
`During prosecution, the examinerexplicitly makes note of this fact and indicates that the patentee was well aware
`of the knowledgeofthe art by stating: “in the Background section of the instant application, the applicant describes
`the use of ALA composition for photodynamic therapyis well knownin theart.”
`
`In fact, in Dragieva (2004), the method was so well established that it was used as the control in experiments
`investigating the use of an alternate photosensistizer.
`
`© 2021 INTERNATIONAL PATENT REVIEWS, LLC
`ALL RIGHTS RESERVED
`
`6
`
`

`

`The supposed differentiating factor for the ‘567 over the prior art was the addition of an element relating to
`“removing …[a] low density polyethylene barrier within 3 hours and then applying light to …[a] treatment area.”
`However, this so-called novel element was very well known in the art at the time of the invention.
`
`More specifically, the use of topical 5-ala in photodynamic treatments may be traced back at least as far as 1990.
`MacCormack lists no fewer than 46 studies on the use of 5-ala/mal for the treatment of actinic keratoses and/or
`acne prior to 2008 (see Table I extracted from MacCormack 2008, below). Further, many of these citations used
`occlusive coverings to enhance 5-ala/mal uptake.
`
`Lack of disclosure of the prior art during prosecution of the ‘567 was rampant.
`
`Ozog discloses the state of the art of 5-ALA PDT as of 2016 (Table 4 below) and presents 93 cited references.
`Only one of the citations from Ozog (Schmieder, describing a clinical trial, red arrow below) is mentioned on the
`face of the patent or during prosecution. NONE of the other 92 state of the art references from Ozog are
`mentioned on the face of the patent nor during prosecution:
`
`
`
`
`Ozog 2016
`
`
`
`
`7
`
`

`

`
`
`
`Wolf 1993
`Fink-Puches 1997
`Varma 2001
`
`Goldman 2003
`Alexiades 2003
`Touma 2004*
`Tschen 2006
`
`
`As mentioned, from MacCormack, NONE of the citations listed in Table 1 entitled “Studies on the Use of 5-ALA/MAL
`PDT for the Treatment of Actinic Keratoses” (below) is found on the face of the patent nor cited during prosecution:
`
`Kennedy 2009
`Szeimies 1996
`Dijkstra 2001
`Szeimies 2002
`Smith 2003
`
`Avram 2004
`
`Morton 2006
`
`
`Of these omitted citations, attention is called to at least Kennedy 2009, Fink-Puches 1997, Jeffes 1997, and
`Alexiades 2003 as being particularly pertinent to the prior art (indicated below in red).
`
`
`Calzaver-Pinton 1993
`Jeffes 1997
`
`Jeffes 2001
`
`Freeman 2003
`Dragieva 2003a, 2003b
`Kim 2005
`
`Perrett 2007
`
`
`Fijan 1995
`
`Kurwa 1999
`Ruiz-Rodriquez 2002
`Pariser 2003
`Piacquadio 2004
`Tarstedt 2005
`
`
`
`
`
`
`
`8
`
`

`

`
`
`Ozog is the primary document cited for invalidating prior art in the claim chart, below. Ozog is a consensus
`document from a panel of experts on the understanding of the state of the art and use of 5-ALA PDT. It was
`published in July 2016, at least a year and a half before the priority date of the ‘567. Ozog is neither cited not
`mentioned during prosecution of the application resulting in the issuance of the ‘567 patent.
`
`Ozog states as follows:
`
`
`The American Society of Dermatologic Surgery (ASDS) periodically develops
`consensus documents for its members concerning various aspects of
`dermatologic surgery. Advances in photodynamic therapy (PDT) have been many
`and PDT use has been established in a variety of skin conditions.
`
`OBJECTIVE: The ASDS board of directors proposed a committee of experts in
`the field to develop consensus documents on different treatments. An expert panel
`reviewed the literature on PDT and discussed the findings. The consensus was
`reached with evidence-based recommendations on different clinical
`applications for PDT. (Abstract; emphasis added)
`
`
`Ozog specifically delineates the following procedures, particularly pertinent to the prior art:
`
`
`
`
`
`
`
`
`
`
`
`
`
`9
`
`

`

`
`
`
`
`The Table below is a very brief summary of some of the pertinent prior art exemplary of various elements of the
`claims in the ‘567.
`
`
`
`5-ALA or
`MAL
`5-ALA
`
`Topical
`application
`
`
`
`
`Publication
`
`Piacquadio
`2004
`Alexiades-
`Armenakas
`2003
`Kurwa 1999
`
`5-ALA
`
`5-ALA
`
`Occlusion
`
`3 hrs
`
`Light
`
`Hand/Forearm
`
`
`
`
`
`Blue
`
` gauze
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Saran wrap
`
`
`
`
`plastic wrap
`
`
`plastic film
`
`
`
` Tegaderm
`
`
`Saran wrap
`
`
`
`
`
`4 hrs
`
`
`
`
`
`
`
`
`
`
`
`
`
`4 hrs
`
`6 hrs
`
`4 hrs
`
`3 hrs
`
`
`
`
`
`4 hrs
`
`PDL (595
`nm)
`
`Red (580 to
`740 nm)
`Red
`(634 nm)
`Red (600-
`700 nm)
`Red (550-
`700 nm)
`
`
`
`
`Blue
`
`Red (615
`nm)
`
`Red 580-
`740 nm
`Red 640 nm
`
`Blue
`
`Blue and
`Red
`Red 570 nm
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Tarstedt 2005
`
`MAL
`
`Dragieva 2003
`
`MAL
`
`Hongcharu
`2000
`Jeffes 1997
`
`Ozog
`
`Ruiz-
`Rodriquez
`2002
`Szeimes 1996
`
`Varma 2000
`
`Sakamoto
`2008
`MacCormack
`
`5-ALA
`
`5-ALA
`
`5-ALA
`
`5-ALA
`
`5-ALA
`
`5-ALA
`
`5-ALA
`
`5-ALA
`
`Wolf 1993
`
`5-ALA
`
`
`
`
`
`
`
`10
`
`

`

`Ground I
`
`U.S. 10357567 B1
`
`Claims 1, 2, and 4-9 are obvious under35 U.S.C § 103(a) over the prior art of Ozog in view
`of Sakamoto.
`
`U.S. 10357567
`1. A method of enhancing penetration
`of a topical composition of 5-
`aminolevulinic acid (ALA) into tissue
`for photodynamic therapy, the
`method comprising:
`
`Ozog in view of Sakamoto
`Ozog teaches a method of enhancing penetration (“occlusion
`has been used to increase penetration.” Pg. 808, right
`column, top) of a topical composition of 5-aminolevulinic acid
`(ALA)into tissue for photodynamic therapy (“The application
`of the topical ALA solution...” pg. 808 left column, bottom;
`“The main types of topical photosensitizer prodrugs used for
`PDT are 5-aminolevulinic acid (5-ALA)orits derivatives.”
`Pg. 804 left column, bottom).
`
`
`
`topically applying ALA to a
`treatment area to be treated with
`photodynamic therapy;
`
`Ozog teaches topically applying ALA to a treatment area to be
`treated with photodynamic therapy (“The application of the
`topical ALA solution...” pg. 808 left column, bottom; “The main
`types of topical photosensitizer prodrugs used for PDT
`are 5-aminolevulinic acid (5-ALA)orits derivatives.” Pg.
`804 left column, bottom).
`
`after the ALA is applied to the
`treatment area, covering the
`treatment area with a low density
`polyethylene barrier prior to light
`treatment to minimize
`transepidermal water loss from the
`treatment area; and
`
`Ozog teaches after the ALA is applied to the treatment area,
`covering the treatmentarea with a plastic wrap-type, occlusive
`barrier prior to light treatment to minimize transepidermal water
`loss from the treatment area; (“For nonfacial areas, such as the
`extremities, occlusion has been used to increase
`penetration. This can be accomplished with plastic wrap or
`someother nonporousflexible material placed over the targeted
`area after the ALA has been applied.” Pg. 808 right column top)
`
`light to the treatment area (“A recent multicenter
`
`
`Ozog does notspecifically teach the plastic wrap-type, occlusive
`barrier is low density polyethylene. However low density
`polyethylene barriers to enhance penetration were well known
`in the art at the time of the invention as described by
`Sakamoto. Sakamoto teaches PDTin which after ALA is applied
`to the treatment area, covering the treatment area with a low
`density polyethylene barrier prior to light treatment to minimize
`transepidermal waterloss from the treatment area (para [0106]
`“An occlusive, transparent plastic mask or covering such
`as, e.g., Saran® wrapora transparent occlusive ointment
`may optionally be placed, sprayed or spread on the skin.)
`
`Saran wrap wasa well knownlow density polyethylene material.
`It would have been obvious to POSAthat a low density
`polyethylene barriers such as Saran® wrap could have been
`used to cover the area of application to minimize tranepidermal
`waterloss as a method to increase penetration of 5-ALA as
`described without undue experimentation according to the
`method of Ozog in view of Sakamoto.
`
`[Other references to plastic wrap or Saran wrapcanbe readily
`
`removing the low density
`polyethylene barrier within 3 hours
`
`Ozog teaches removing the occlusive barrier within 3 hours and
`ing
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`ALL RIGHTS RESERVED
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`UR ye yi
`and then applying light to the
`treatment area.
`
`2. A method as set forth in claim 1,
`wherein the low density
`polyethylene barrier is removed
`from the treatment area within 3
`hours and thenbluelight is applied
`to the treatment area for a 10
`J/cm2 light dose.
`
`3. The method ofclaim 1, wherein a
`maximum plasma concentration of
`ALA following application ofthe ALA
`Is less than about 110 ng/mL.
`4. A method of enhancing penetration
`of a topical composition of 5-
`aminolevulinic acid (ALA) into tissue
`for photodynamic therapy, the
`method comprising:
`
`topically applying ALA to a
`treatment area to be treated with
`photodynamic therapy; and
`
`after the ALA is applied to the
`treatment area, covering the
`treatment area with a low density
`polyethylene barrier prior to light
`treatment to minimize
`transepidermal water loss from the
`treatment area,
`
`U.S. 10357567 Bi
`
`Ozogin view of Sakamoto
`randomized study found the median AK clearance rate at 12
`weeks to be 88.7%for extremities, when treated with ALA
`underocclusion for 3 hours and irradiated with blue
`light (10 J/cm2)” pg. 808, right column, middle; “After
`incubation, the targeted area may be gently
`washed with water and a cleanser.” pg. 808 right column,
`bottom. Further “the targeted area may be gently washed”
`following incubation implies that the barrier has been
`removed.).
`
`See also Schmieder et 2/2012
`The method of claim 1 is obvious, as described above. Further,
`Ozog teaches the occlusive barrier is removed from the
`treatment area within 3 hours and thenbluelight is applied to
`the treatment area for a 10 J/cm2light dose (“A recent
`multicenter randomized study found the median AK clearance
`rate at 12 weeks to be 88.7%for extremities, when treated
`with ALA underocclusion for 3 hours andirradiated with
`blue light (10 J/cm2)” pg. 808, right column, middle).
`
`Not on FDA label under Section 2 “Dosage andAdministration”
`as being required for treatment.
`
`enhancepenetration of ALA were well knownin the art at the
`
`Ozog teaches a method of enhancing penetration (“occlusion
`has been used to increase penetration.” Pg. 808, right
`column, top) of a topical composition of 5-aminolevulinic acid
`(ALA)into tissue for photodynamic therapy (“The application
`of the topical ALA solution...” pg. 808 left column, bottom;
`“The main types of topical photosensitizer prodrugs used for
`PDTare 5-aminolevulinic acid (5-ALA)orits derivatives.”
`Pg. 804 left column, bottom).
`
`Ozog teaches topically applying ALA to a treatment area to be
`treated with photodynamic therapy (“The application of the
`topical ALA solution...” pg. 808 left column, bottom; “The main
`types of topical photosensitizer prodrugs used for PDT
`are 5-aminolevulinic acid (5-ALA)orits derivatives.” Pg.
`804 left column, bottom).
`
`Ozog teaches after the ALA is applied to the treatment area,
`covering the treatment area with a plastic wrap-type, occlusive
`barrier prior to light treatment to minimize transepidermal water
`loss from the treatment area; ("For nonfacial areas, such as the
`extremities, occlusion has been used to increase penetration.
`This can be accomplished with plastic wrap or some other
`nonporousflexible material placed over the targeted area after
`the ALA has been applied.” Pg. 808, right column, top)
`
`Ozog does not specifically teach the plastic wrap-type, occlusive
`barrier is specifically low density polyethylene. However low
`density polyethylene plastic wrap-type, occlusive barriers to
`
`© 2021 INTERNATIONAL PATENT REVIEWS, LLC
`ALL RIGHTS RESERVED
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`U.S. 10357567
`
`wherein the treatment area is
`located on a hand or a forearm.
`
`A method asset forth in claim 4,
`wherein the low density
`polyethylene barrier is removed
`from the treatment area and then
`red light is applied to the treatment
`area for a 10 to 75 J/cm2light
`dose.
`
`nm, 70 J/cm2) pg. 820 left column top).
`
`
`U.S. 10357567 Bi
`
`Ozogin view of Sakamoto
`time of the invention as described by Sakamoto. Sakamoto
`specifically teaches the plastic wrap-type, occlusive barrieris a
`low density polyethylene barrier covering the treatment area
`with prior to light treatment to minimize transepidermal water
`loss from the treatment area and is employed after ALA is
`applied to the treatment area, (para [0106] “An occlusive,
`transparent plastic mask or covering such as, e.g., Saran®
`wrapor a transparentocclusive ointment may optionally be
`placed, sprayed or spread on theskin.)
`
`It would have been obvious to POSA that a low density
`polyethylene barriers such as Saran® wrapcould have been
`used to cover the area of application to minimize tranepidermal
`water loss as a method to increase penetration of 5-ALA as
`described without undue experimentation according to Ozog in
`further view of Sakamoto.
`
`Ozog teaches the treatment area is located on a hand or a
`forearm (Figure 5 pg. 814; “For nonfacial areas, such as
`the extremities, occlusion has been used to increase
`penetration.” Pg. 808, right column top; “Sixteen
`patients with 542 AKs in field-cancerized skin of the
`scalp, chest, and extremities were treated.” Pg. 812, left
`column middle).
`The method of claim 4 is obvious as described above. Further,
`Ozog teaches removing the barrier from the treatment area
`prior to phototherapy area (“A recent multicenter randomized
`study found the median AK clearance rate at 12 weeks to be
`88.7%for extremities, when treated with ALA under
`occlusionfor 3 hours andirradiated with blue light (10
`J/cm2)” pg. 808, right column, middle; “After incubation, the
`targeted area may be gently washed with water and a
`cleanser.” pg. 808 right column, bottom. Wherein “the targeted
`area may be gently washed”following incubation implies that
`the barrier has been removed. [See also Schmieder et a/
`2012]), and further that red light is applied to the treatment
`area following theinitial treatment interval of less than 3 hours.
`(Table 4, pg. 811; “...compared the efficacy of ALA-PDT with
`that of MAL-PDT...” ... Both photosensitizers were applied for 3
`hours underocclusion, followed by irradiation with red light
`(635 nm, 37 J/cm2) pg. 817 right column middle; “red light
`(635 nm)is used for thicker lesions because it has a greater
`than 2-mm penetration.” Pg. 806, right column bottom; “Red
`light requires a longerirradiation period because it does not
`excite PpIX as efficiently as blue light. ... In fact, there is
`evidence to support that cumulative light doses of greater than
`40 J/cm2 can deplete all available oxygen sources during the
`oxidation reaction, making higher doses of energy during PDT
`unnecessary.” Pg. 807 right column, bottom; (3 hours of
`incubation with illumination with broad-spectrum red light; 75
`J/cm2” pg. 810 left column middle.; “Red light (630 nm)
`irradiation was used for both ALA and MAL; range 37 to 80 J/cm
`pg. 812 left column bottom; Figure 8; “ALA wasapplied under
`occlusion for 4 hour beforeirradiation with red light (590-700
`
`© 2021 INTERNATIONAL PATENT REVIEWS, LLC
`ALL RIGHTS RESERVED
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`U.S. 10357567
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`6. The method asset forth in claim 4,
`wherein the treatment area is a
`dorsal surface of the hand.
`
`7. The method asset forth in claim 4,
`wherein the treatment area is a
`dorsal surface of the forearm.
`
`8. A method of using 5-aminolevulinic
`acid (ALA) and a low density
`polyethylene barrier, comprising:
`
`
`
`U.S. 10357567 Bi
`
`Ozogin view of Sakamoto
`
`Claim 4 is obvious as above. Further, Ozog teaches the
`treatment area is a dorsal surface of the hand. (Figure 5 pg.
`814).
`
`minimize transepidermal water loss as a method to increase
`
`Claim 4 is obvious as above. Ozog does not specifically teach
`the treatment area is a dorsal surface of the forearm. However,
`Ozog does specifically teach “treatment of extremities”, (“For
`nonfacial areas, such as the extremities, occlusion has been
`used to increase penetration.” Pg. 808, right column top;
`“Sixteen patients with 542 AKs in field-cancerized skin of the
`scalp, chest, and extremities were treated.” Pg. 812, left
`column middle).
`
`It would have been readily obvious to POSA that treatment of
`the dorsal forearm would have beenavailable as a type of well
`known treatmentof extremities.
`
`[See also Schmeider whichspecifically teaches the treatment
`area is a dorsal surface of a forearm.
`Ozog teaches a method using 5-aminolevulinic acid (ALA) (“The
`application of the topical ALA solution...” pg. 808 left
`column, bottom; “The main types of topical photosensitizer
`prodrugs used for PDT are 5-aminolevulinic acid (5-ALA) or
`its derivatives.” Pg. 804 left column, bottom) and a plastic
`wrap-type, occlusive barrier (“Occlusion has been used to
`increase penetration.” This can be accomplished with plastic
`wrap or someother nonporousflexible material placed over the
`targeted area after the ALA has been applied. Pg. 808, right
`column, top)
`
`Ozog does not specifically teach the barrier is low density
`polyethylene. However low density polyethylene barriers to
`enhance penetration were well knownin the art at the time of
`the invention as described by Sakamoto. Sakamoto teaches PDT
`in which after ALA is applied to the treatment area, covering the
`treatment area with a low density polyethylene barrier prior to
`light treatment to minimize transepidermal waterloss from the
`treatment area (para [0106] “An occlusive, transparent
`plastic mask or covering such as, e.g., Saran® wrapor a
`transparent occlusive ointment may optionally be placed,
`sprayed or spread ontheskin.)
`
`Saran wrap was a well-known low density polyethylene
`material. It would have been obvious to POSA that a low
`density polyethylene barriers such as Saran® wraporsimilar
`could have been used to coverthe area of application to
`
`© 2021 INTERNATIONAL PATENT REVIEWS, LLC
`ALL RIGHTS RESERVED
`
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`U.S. 10357567 Bi
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`U.S. 10357567
`
`Ozogin view of Sakamoto
`penetration of 5-ALA as described by Sakamoto without undue
`experimentation.
`
`contacting a treatmentsite with a
`composition comprising the ALA so
`as to wet the treatmentsite;
`
`Ozog teaches contacting a treatment site with a composition
`comprising the ALA so as to wet the treatmentsite (“The
`application of the topical ALA solution...” pg. 808 left
`column, bottom; “The main types of topical photosensitizer
`prodrugs used for PDT are 5-aminolevulinic acid (5-ALA) or
`its derivatives.” Pg. 804 left column, bottom; “In the United
`States, ALA is available as a 20%solution and is marketed
`underthe trade name Levulan (DUSA Pharmaceuticals, Inc.,
`Wilmington, MA). It is FDA approved since 1999...” pg. 806,left
`column, middle)
`
`According to the specifications ofthe
`‘567, the term “wetting”means simply
`to apply a topical composition ofALA to
`the surface ofthe skin and nothing
`more. "The method includes contacting
`a treatmentsite with a composition
`comprising the ALA so as to wet the
`treatment site”(col 2 In 61—63) and “In
`one embodiment, ALA may be applied
`in a topical composition with a
`concentration of20 % . The ALA
`admixture is topically applied to the
`lesions using a point applicator to
`control dispersion ofthe ALA admixture,
`in at least one embodiment, so as to
`achieve a substantially uniform wetting
`ofthe lesion surface with the ALA by
`contacting the ALA with the lesion
`surface.”(col 9 In 11-18)
`
`
`Ozog also teachesalternative methods to wet the treatmentsite
`(“Many methodsexist for pretreatment preparation of skin-
`cleansing regimens. Cleaning allows for a more uniform
`penetration of the ALA and subsequent photoactivation....
`Isopropy