Paper No. 1
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`__________________
`
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`BIOFRONTERA INCORPORATED,
`
`BIOFRONTERA BIOSCIENCE GMBH,
`
`BIOFRONTERA PHARMA GMBH,
`
`AND
`
`BIOFRONTERA AG
`
`Petitioner
`
`v.
`
`DUSA PHARMACEUTICALS, INC.
`
`Patent Owner
`__________________
`
`
`Inter Partes Review No. IPR2022-00056
`
`Patent 10,357,567
`
`__________________
`
`
`
`PETITION FOR INTER PARTES REVIEW UNDER 35 U.S.C. 312
`
`
`
`
`
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`

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`IPR2022-00056
`Patent 10,357,567
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`V. 
`
`Table of Contents
`INTRODUCTION ........................................................................................... 1 
`I. 
`II.  MANDATORY NOTICES ............................................................................. 3 
`A. 
`Real Party in Interest (37 C.F.R. § 42.8(b)(1)) ..................................... 3 
`B. 
`Related Matters (37 C.F.R. § 42.8(b)(2)) .............................................. 3 
`C. 
`Lead and Back-Up Counsel (37 C.F.R. § 42.8(b)(3)) ........................... 4 
`D. 
`Service Information (37 C.F.R. § 42.8(b)(4)) ....................................... 4 
`E. 
`Payment of Fees (37 C.F.R. §§ 42.15(a) and 42.103(a)) ...................... 4 
`III.  GROUNDS FOR STANDING (37 C.F.R. § 42.104(a)) ................................. 4 
`IV.  STATEMENT OF PRECISE RELIEF REQUESTED FOR EACH
`CLAIM CHALLENGED ................................................................................ 5 
`A. 
`Claims for Which Review Is Requested (37 C.F.R. §
`42.104(b)(1)) ......................................................................................... 5 
`Statutory Grounds of Challenge (37 C.F.R. § 42.104(b)(2)) ................ 5 
`B. 
`FIELD OF TECHNOLOGY ........................................................................... 8 
`A. 
`Photodynamic Therapy ......................................................................... 9 
`B. 
`5-Aminolevulinic Acid (ALA) ............................................................ 10 
`C. 
`Photodynamic Therapy Light Sources ................................................ 11 
`D. 
`Photodynamic Therapy Treatment of Actinic Keratosis ..................... 14 
`E. 
`Use of Occlusion to Minimize Transepidermal Water Loss and
`Enhance Penetration of ALA Was Well-Known in the Art ................ 16 
`VI.  THE ’567 PATENT ....................................................................................... 18 
`A. 
`Claims and Specification of the ’567 Patent ....................................... 18 
`B. 
`Prosecution History of the ’567 Patent ............................................... 21 
`C. 
`Claim Construction ............................................................................. 22 
`1. 
`“dorsal surface of the hand” (claim 6) / “dorsal surface of
`the forearm” (claim 7) ............................................................... 22 
`VII.  REASONS FOR THE RELIEF REQUESTED UNDER 37 C.F.R. §§
`42.22(A)(2) AND 42.104(B)(4) .................................................................... 24 
`A. 
`The Scope and Content of the Prior Art .............................................. 24 
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`IPR2022-00056
`Patent 10,357,567
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`1. 
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`2. 
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`3. 
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`2. 
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`3. 
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`4. 
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`5. 
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`The Prior Art Teaches that Occlusive Barriers Like
`LDPE Minimize Transepidermal Water Loss .......................... 24 
`The Prior Art Teaches Removal of Occlusive Coverings
`for Photodynamic Therapy Prior to Illumination ..................... 26 
`The Prior Art Teaches PDT Treatment using LDPE
`Occlusive Barriers on the Hands and Forearms........................ 27 
`Level of Ordinary Skill in the Art ....................................................... 28 
`Ground 1 – Claims 1-4 and 6-10 Are Unpatentable as
`Anticipated by Willey ......................................................................... 28 
`1. 
`Claim 1pre: “A method of enhancing penetration of a
`topical composition of 5-aminolevulinic acid (ALA) into
`tissue for photodynamic therapy, the method
`comprising:” .............................................................................. 28 
`Claim 1a: “topically applying ALA to a treatment area to
`be treated with photodynamic therapy” .................................... 29 
`Claim 1b: “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” ......... 29 
`Claim 1c: “removing the low density polyethylene barrier
`within 3 hours and then applying light to the treatment
`area.” ......................................................................................... 31 
`Claim 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 then blue light is
`applied to the treatment area for a 10 J/cm2 light dose.” .......... 32 
`Claim 3: “The method of claim 1, wherein a maximum
`plasma concentration of ALA following application of
`the ALA is less than about 110 ng/mL.” .................................. 33 
`Claim 4pre: “A method of enhancing penetration of a
`topical composition of 5-aminolevulinic acid (ALA) into
`tissue for photodynamic therapy, the method
`comprising:” .............................................................................. 34 
`Claim 4a: “topically applying ALA to a treatment area to
`be treated with photodynamic therapy; and” ............................ 34 
`Claim 4b: “after the ALA is applied to the treatment area,
`covering the treatment area with a low density
`ii
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`6. 
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`7. 
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`8. 
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`9. 
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`B. 
`C. 
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`IPR2022-00056
`Patent 10,357,567
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`polyethylene barrier prior to light treatment to minimize
`transepidermal water loss from the treatment area,” ................ 35 
`10.  Claim 4c: “wherein the treatment area is located on a
`hand or a forearm.” ................................................................... 35 
`11.  Claim 6: “The method as set forth in claim 4, wherein the
`treatment area is a dorsal surface of the hand.” / Claim 7:
`“The method as set forth in claim 4, wherein the
`treatment area is a dorsal surface of the forearm.” ................... 35 
`12.  Claim 8pre: “A method of using 5-aminolevulinic acid
`(ALA) and a low density polyethylene barrier,
`comprising:” .............................................................................. 36 
`13.  Claim 8a: “contacting a treatment site with a composition
`comprising the ALA so as to wet the treatment site;” .............. 36 
`14.  Claim 8b: “following wetting of the treatment site,
`covering the wetted treatment site with the low density
`polyethylene barrier;” ............................................................... 37 
`15.  Claim 8c: “removing the low density polyethylene barrier
`so as to expose the treatment site; and” .................................... 38 
`16.  Claim 8d: “illuminating the exposed treatment site with
`an illuminator so as to deliver a 10 J/cm2 dose of blue
`light.” ......................................................................................... 38 
`17.  Claim 9: “The method of claim 8, wherein the low
`density polyethylene barrier is removed no later than
`three hours after the treatment site is covered.” ........................ 38 
`18.  Claim 10: “The method of claim 8, further comprising:
`positioning the treatment site between two inches and
`four inches from a surface of the illuminator.” ......................... 39 
`D.  Ground 2 – Claim 3 Is Unpatentable as Obvious Over Willey
`Combined with Ameluz ...................................................................... 39 
`1. 
`Claim 3: “The method of Claim 1, wherein a maximum
`plasma concentration of ALA following application of
`the ALA is less than about 110 ng/mL.” .................................. 39 
`Ground 3 – Claim 5 Is Unpatentable as Obvious Over Willey
`Combined with Sotiriou ...................................................................... 43 
`1. 
`Claim 5: “A method as set forth in claim 4, wherein the
`low density polyethylene barrier is removed from the
`
`E. 
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`IPR2022-00056
`Patent 10,357,567
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`2. 
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`3. 
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`4. 
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`5. 
`
`treatment area and then red light is applied to the
`treatment area for a 10 to 75 J/cm2 light dose.” ....................... 43 
`Ground 4 – Claims 1-9 Are Unpatentable as Anticipated by
`Noven Pharma ..................................................................................... 45 
`1. 
`Claim 1pre: “A method of enhancing penetration of a
`topical composition of 5-aminolevulinic acid (ALA) into
`tissue for photodynamic therapy, the method
`comprising:” .............................................................................. 45 
`Claim 1a: “topically applying ALA to a treatment area to
`be treated with photodynamic therapy” .................................... 46 
`Claim 1b: “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” ......... 46 
`Claim 1c: “removing the low density polyethylene barrier
`within 3 hours and then applying light to the treatment
`area.” ......................................................................................... 47 
`Claim 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 then blue light is
`applied to the treatment area for a 10 J/cm2 light dose.” .......... 49 
`Claim 3: “The method of claim 1, wherein a maximum
`plasma concentration of ALA following application of
`the ALA is less than about 110 ng/mL.” .................................. 51 
`Claim 4pre: “A method of enhancing penetration of a
`topical composition of 5-aminolevulinic acid (ALA) into
`tissue for photodynamic therapy, the method
`comprising:” .............................................................................. 52 
`Claim 4a: “topically applying ALA to a treatment area to
`be treated with photodynamic therapy; and” ............................ 53 
`Claim 4b: “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,” ................ 53 
`10.  Claim 4c: “wherein the treatment area is located on a
`hand or a forearm.” ................................................................... 53 
`
`6. 
`
`7. 
`
`8. 
`
`9. 
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`iv
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`F. 
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`IPR2022-00056
`Patent 10,357,567
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`11.  Claim 5: “A method as set 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/cm2 light dose.” ........................ 53 
`12.  Claim 6: “The method as set forth in claim 4, wherein the
`treatment area is a dorsal surface of the hand.” / Claim 7:
`“The method as set forth in claim 4, wherein the
`treatment area is a dorsal surface of the forearm.” ................... 54 
`13.  Claim 8pre: “A method of using 5-aminolevulinic acid
`(ALA) and a low density polyethylene barrier,
`comprising:” .............................................................................. 55 
`14.  Claim 8a: “contacting a treatment site with a composition
`comprising the ALA so as to wet the treatment site;” .............. 56 
`15.  Claim 8b: “following wetting of the treatment site,
`covering the wetted treatment site with the low density
`polyethylene barrier;” ............................................................... 57 
`16.  Claim 8c: “removing the low density polyethylene barrier
`so as to expose the treatment site; and” .................................... 57 
`17.  Claim 8d: “illuminating the exposed treatment site with
`an illuminator so as to deliver a 10 J/cm2 dose of blue
`light.” ......................................................................................... 57 
`18.  Claim 9: “The method of claim 8, wherein the low
`density polyethylene barrier is removed no later than
`three hours after the treatment site is covered.” ........................ 58 
`G.  Ground 5 – Claim 3 Is Unpatentable as Obvious Over Noven
`Pharma Combined with Fauteck ......................................................... 59 
`1. 
`Claim 3: “The method of claim 1, wherein a maximum
`plasma concentration of ALA following application of
`the ALA is less than about 110 ng/mL.” .................................. 59 
`H.  Ground 6 – Claim 10 Is Unpatentable as Obvious Over Noven
`Pharma Combined with the BLU-U Operating Manual ..................... 62 
`1. 
`Claim 10: “The method of claim 8, further comprising:
`positioning the treatment site between two inches and
`four inches from a surface of the illuminator.” ......................... 62 
`VIII.  Any Secondary Considerations PO May Raise Do Not Overcome the
`Prima Facie Case of Obviousness ................................................................. 63 
`1. 
`No Unexpected Results ............................................................. 63 
`v
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`IX.  CONCLUSION .............................................................................................. 64 
`TX. CONCLUSION... eee eeeeeeseeeseeeseeeseeeeaeeeaeeeseeesaeeeaeeesaecsaessaeeeseeeseeeseaeees 64
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`IPR2022-00056
`IPR2022-00056
`Patent 10,357,567
`Patent 10,357,567
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`Exhibit
`
`Petitioner’s Exhibit List
`Description
`
`IPR2022-00056
`Patent 10,357,567
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`1001
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`1002
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`1003
`
`1004
`
`1005
`
`1006
`
`1007
`
`1008
`
`1009
`
`1010
`
`1011
`
`1012
`
`U.S. Patent No. 10,357,567 (“the ’567 patent”)
`
`Excerpts from U.S. Patent Application No. 15/869,164 (“the ’164
`Application”)
`
`Declaration of Dr. Howard Rogers MD, PHD
`
`CV of Dr. Howard Rogers MD, PHD
`
`PCT Publication No. WO 96/06602 (“Noven Pharma”)
`
`Sakamoto FH, Torezan L, Anderson RR. Photodynamic therapy
`for acne vulgaris: a critical review from basics to clinical
`practice: part II. Understanding parameters for acne treatment
`with photodynamic therapy. J Am Acad Dermatol. 2010
`Aug;63(2):195-211 (“Sakamoto”)
`
`Berardesca E, Vignoli GP, Fideli D, Maibach H. Effect of
`occlusive dressings on the stratum corneum water holding
`capacity. The American Journal of the Medical Sciences. 1992
`Jul;304(1):25-28 (“Berardesca”)
`
`Fauteck JD, Ackermann G, Birkel M, Breuer M, Moor AC,
`Ebeling A, Ortland C. Fluorescence characteristics and
`pharmacokinetic properties of a novel self-adhesive 5-ALA patch
`for photodynamic therapy of actinic keratoses. Arch Dermatol
`Res. 2008 Feb;300(2):53-60 (“Fauteck”)
`
`U.S. Patent Publication No. US2009/0324727 A1 (“Biofrontera”)
`
`Ameluz® Prescribing Information (2016) (“Ameluz”)
`
`Levulan® Label (2002)
`
`Blu-U® Operating Manual (2006)
`
`vii
`
`
`
`
`
`

`

`
`
`1013
`
`1014
`
`1015
`
`1016
`
`1017
`
`1018
`
`1019
`
`1020
`
`IPR2022-00056
`Patent 10,357,567
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`Willey A, Anderson RR, Sakamoto FH. Temperature-modulated
`photodynamic therapy for the treatment of actinic keratosis on
`the extremities. Dermatologic Surgery. 2014 Oct;40(10):1094-
`1102. (“Willey”)
`
`Calderhead RG. Light-emitting diode phototherapy in
`dermatological practice in lasers in dermatology and medicine.
`Lasers in Dermatology and Medicine. 2011 Aug:231-265.
`(“Calderhead”)
`
`Palm M., Goldman PM. Aminolevulinic acid: actinic keratosis
`and photorejuvenation. In: Gold M.H., editor. Photodynamic
`Therapy in Dermatology. Springer Science and Business Media,
`LLC. 2011 Nov:5-30. (“Palm”)
`
`MacCormack MA. Photodynamic therapy in dermatology: an
`update on applications and outcomes. Semin Cutan Med Surg.
`2008 Mar;27(1):52-62. (“MacCormack”)
`
`Sotiriou E, Apalla Z, Maliamani F, Zaparas N, Panagiotidou D,
`Ioannides D. Intraindividual, right-left comparison of topical 5-
`aminolevulinic acid photodynamic therapy vs. 5% imiquimod
`cream for actinic keratoses on the upper extremities. J Eur Acad
`Dermatol Venereol. 2009 Sep;23(9):1061-5. (“Sotiriou”)
`
`Bissonnette R. Photodynamic therapy. In: Gold M.H., editor.
`Photodynamic Therapy in Dermatology. Springer Science and
`Business Media, LLC; New York, NY, USA: 2011. pp. 221–229.
`(“Bissonnette”)
`
`McLaren G. Photodynamic therapy. In; Pfenninger and Fowler's
`procedures for primary care. Third Ed. Mosby Elsevier;
`Philadelphia, PA: 2011. pp 397-400. (“McLaren”)
`
`Harris DR. Percutaneous absorption and the surface area of
`occluded skin: a scanning electron microscopic study. British
`Journal of Dermatology. 1974; 91(27-32). (“Harris”)
`
`1021
`
`Levulan® Label (2009)
`
`
`
`viii
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`

`

`IPR2022-00056
`Patent 10,357,567
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`Wachowska et al., Aminolevulinic acid (ALA) as a prodrug in
`photodynamic therapy of cancer. Molecules. 2011 May; 16(5):
`4140-4164. (“Wachowska”)
`
`Agostinis et al. Photodynamic therapy of cancer: an update. CA:
`A Cancer Journal for Clinicians. 2011 May; 61(4):250-281.
`(“Agostinis”).
`
`Wolf P., Rieger E. and Kerl H. Topical photodynamic therapy
`with endogenous porphyrins after application of 5-
`aminolevulinic acid: an alternative treatment modality for solar
`keratoses, superficial squamous cell carcinomas, and basal cell
`carcinomas? Journal of the American Academy of Dermatology
`28.1 (1993): 17-21 (“Wolf”)
`
`Jeffes E., McCullough J., Weinstein G., Fergin P., Nelson J.,
`Shull T., Simpson K., Bukaty L., Hoffman W., Fong N.
`Photodynamic therapy of actinic keratosis with topical 5-
`aminolevulinic acid. A pilot dose-ranging study. Arch Dermatol.
`1997 Jun;133(6):727-32 (“Jeffes”)
`
`Hongcharu W., Taylor C., Chang, Y., Aghasi, D., Suthamjariya,
`K., Anderson, R. Topical ALA-photodynamic therapy for the
`treatment of acne vulgaris. J Invest Dermatol. 2000
`Aug;115(2):183-92 (“Hongcharu”)
`
`Ozog, D., Rkein, A., Fabi, S., Gold M., Goldman, M., Lowe, N.,
`Martin, G., Munavalli, G. Photodynamic therapy: A clinical
`consensus guide. Dermatol Surg. 2016 Jul;42(7):804-27
`(“Ozog”)
`
`Aktilite CL128 Operators Manual with Metvixia
`
`DUSA Levulan Press Release
`
`European Medicines Agency CHMP Assessment Report
`(excerpts)
`
`Affidavit of Duncan Hall
`
`ix
`
`
`
`1022
`
`1023
`
`1024
`
`1025
`
`1026
`
`
`1027
`
`1028
`
`1029
`
`1030
`
`1031
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`
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`

`

`
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`1032
`
`1033
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`1034
`
`1035
`
`1036
`
`1037
`
`IPR2022-00056
`Patent 10,357,567
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`Willey Pubmed Website Database Listing
`
`Sotiriou Pubmed Website Database Listing
`
`Fauteck Europe PMC Website Database Listing
`
`Rick K, Sroka R, Stepp H, Kriegmair M, Huber RM, Jacob K,
`Baumgartner R. Pharmacokinetics of 5-aminolevulinic acid-
`induced protoporphyrin IX in skin and blood. J Photochem
`Photobiol B. 1997 Oct;40(3):313-9 (“Rick”)
`
`International Patent Reviews, LLC review of U.S. Patent No.
`10,357,567 dated July 26, 2021 available at https://patent-
`reviews.com/
`
`News article entitled “DUSA Pharmaceuticals To Pay U.S.
`$20.75 Million To Settle False Claims Act Allegations Relating
`To Promotion Of Unsupported Drug Administration Process”
`available at https://www.justice.gov/opa/pr/dusa-
`pharmaceuticals-pay-us-2075-million-settle-false-claims-act-
`allegations-relating
`
`
`
`x
`
`

`

`Pursuant to 35 U.S.C. §§ 311-319, Biofrontera Incorporated, Biofrontera
`
`IPR2022-00056
`Patent 10,357,567
`
`
`
`Bioscience GmbH, Biofrontera Pharma GmbH, and Biofrontera AG (collectively,
`
`“Petitioner”) hereby respectfully request inter partes review of claims 1–10
`
`(“Challenged Claims”) of U.S. Patent No. 10,357,567 (“the ’567 Patent”), which
`
`issued on July 23, 2019 and is assigned to DUSA Pharmaceuticals, Inc. (“DUSA”
`
`or “PO”). As explained herein, there is a reasonable likelihood that Petitioner will
`
`prevail in establishing that the ʼ567 Patent is unpatentable as anticipated and
`
`obvious.
`
`I.
`
`INTRODUCTION
`Petitioner and PO are competitors in the marketplace for photodynamic
`
`therapy treatments for actinic keratosis—a pre-cancerous skin condition that can
`
`lead to squamous cell carcinoma. Petitioner’s product is marketed in the United
`
`States as Ameluz® and was first approved by the Food and Drug Administration
`
`(“FDA”) in 2016. PO’s product is marketed in the United States as Levulan® and
`
`was first approved by the FDA in 2000.
`
`PO has previously asserted that its photodynamic therapy treatment with
`
`Levulan® was covered by five different patents (EX1021, 015) but the last of PO’s
`
`identified patents expired in October 2017. Facing the prospect of not having any
`
`Orange Book listed patents to protect its Levulan® product, PO pursued a
`
`purportedly new indication for Levulan®: treatment of pre-cancerous lesions on the
`
`1
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`

`

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`hands and forearms using occlusion with low density polyethylene (LDPE) and 5-
`
`IPR2022-00056
`Patent 10,357,567
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`aminolevulinic acid (ALA) photodynamic therapy. EX1021. Concurrently, PO filed
`
`the application that led to the ’567 Patent on January 12, 2018 and requested
`
`prosecution on an expedited basis. But the claims that PO sought in its application
`
`and eventually received in the ’567 Patent reflected a common off-label use of ALA
`
`photodynamic therapy that was already employed by researchers and doctors in the
`
`field for more than a decade. EX1003, ¶¶57-58;71-72.
`
`Noven Pharma filed a PCT application in 1994 disclosing ALA patches for
`
`photodynamic therapy using an occlusive, water-resistant backing material made
`
`from LDPE for treating actinic keratosis on the forearms and elsewhere. EX1005.
`
`Likewise, Palm in 2011 disclosed using ALA photodynamic therapy to treat lesions
`
`on the hands and forearms including the occlusion of areas having thicker lesions
`
`“with Glad Press ‘N Seal®”—a well-known LDPE film. EX1015, 22. Similarly,
`
`Willey in 2014 described the off-label treatment of actinic keratosis (AK) lesions on
`
`the hands and forearms using PO’s product, Levulan®, coupled with occlusion by
`
`Saran® plastic wrap—another, well-known LDPE film. EX1013, 1095. As a result,
`
`the new indication that PO sought to protect with the ’567 Patent—topical ALA
`
`photodynamic therapy using occlusion with LDPE film to enhance penetration of
`
`ALA into tissue, such as that on the hands and forearms—was already well known
`
`in the art prior to January 12, 2018. PO’s attempt to extend patent protection on its
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`2
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`

`

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`Levulan® product by seeking to cover off-label uses that were commonplace in the
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`IPR2022-00056
`Patent 10,357,567
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`prior art should not be countenanced. The ’567 Patent should be held unpatentable.
`
`See EX1036.
`
`II. MANDATORY NOTICES
`A. Real Party in Interest (37 C.F.R. § 42.8(b)(1))
`The real parties-in-interest for Petitioner are Biofrontera Incorporated,
`
`Biofrontera Bioscience GmbH, Biofrontera Pharma GmbH, and Biofrontera AG. No
`
`unnamed entity is funding, controlling, or otherwise has an opportunity to control or
`
`direct this Petition or Petitioner’s participation in any resulting IPR. Also, Petitioner
`
`notes that Biofrontera Inc. has several commonly owned entities, and each of these
`
`entities agrees to be estopped under the provisions of 35 U.S.C. § 315 as a result of
`
`any final written decision in the requested IPR to the same extent that Petitioner is
`
`estopped.
`
`B. Related Matters (37 C.F.R. § 42.8(b)(2))
`At the time of filing of this Petition, Petitioner is unaware of any related
`
`matters concerning the ’567 Patent. Petitioner is presently involved in litigation filed
`
`in the District of Massachusetts originally captioned as Dusa Pharmaceuticals, Inc.
`
`v. Biofrontera Inc. et al. (Civil Action No. 1:18-cv-10568) involving U.S. Patent No.
`
`9,723,991 (“the ’991 Patent”) and U.S. Patent No. 8,216,289 (“the ’289 Patent”).
`
`Neither the ’991 Patent nor the ’289 Patent are in the same family as the ’567 Patent.
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`3
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`
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`C. Lead and Back-Up Counsel (37 C.F.R. § 42.8(b)(3))
`Lead counsel: Lauren L. Fornarotto (Reg. No. 76,470) of McKool
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`IPR2022-00056
`Patent 10,357,567
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`Smith P.C.
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`Back-up counsel: John F. Garvish (pro hac vice to be filed), Geoffrey
`
`L. Smith (pro hac vice to be filed), and Matthew T. Cameron (Reg. No.
`
`74,179) of McKool Smith P.C.
`
`D.
`Service Information (37 C.F.R. § 42.8(b)(4))
`Email: BF-IPR@McKoolSmith.com
`Post: Lauren Fornarotto, MCKOOL SMITH, P.C., One Manhattan West
`
`395 9th Avenue, 50th Floor, New York, New York 10001-8603.
`
`Telephone: (212) 402-9400
`Fax: (212) 402-9444
`Petitioner consents to electronic service.
`E.
`Payment of Fees (37 C.F.R. §§ 42.15(a) and 42.103(a))
`The Office is authorized to charge the fees specified by 37 C.F.R. §§ 42.103(a)
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`and 42.15(a) to Deposit Account No. 50-5723.
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`III. GROUNDS FOR STANDING (37 C.F.R. § 42.104(A))
`Petitioner certifies that the ’567 Patent is available for inter partes review, and
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`that Petitioner is not barred or estopped from requesting an inter partes review
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`challenging the claims on the grounds identified in this Petition.
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`IPR2022-00056
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`IV. STATEMENT OF PRECISE RELIEF REQUESTED FOR EACH
`CLAIM CHALLENGED
`A. Claims for Which Review Is Requested (37 C.F.R. § 42.104(b)(1))
`Petitioner requests the review and cancellation of claims 1–10 (the “Challenged
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`Claims”) of the ’567 Patent.
`
`B.
`Statutory Grounds of Challenge (37 C.F.R. § 42.104(b)(2))
`The Challenged Claims should be canceled for the following reasons:
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`Ground 1: Claims 1-4 and 6-10 are invalid under 35 U.S.C. § 102(a)(1) based
`
`on Willey (EX1013).
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`Ground 2: Claim 3 is invalid under 35 U.S.C. § 103 based on the combination
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`of Willey (EX1013) and the Ameluz® prescribing information (EX1010).
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`Ground 3: Claim 5 is invalid under 35 U.S.C. § 103 based on the combination
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`of Willey (EX1013) and Sotiriou (EX1017).
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`Ground 4: Claims 1-9 are invalid under 35 U.S.C. §§ 102(a)(1) and 102(a)(2)
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`based on PCT Publication No. WO 96/06602 (“Noven Pharma”) (EX1005).
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`Ground 5: Claim 3 is invalid under 35 U.S.C. § 103 based on the combination
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`of Noven Pharma (EX1005) and Fauteck (EX1008).
`
`Ground 6: Claim 10 is invalid under 35 U.S.C. § 103 based on the
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`combination of Noven Pharma (EX1005) and the Blu-U Operating Manual
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`(EX1012).
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`The ’567 Patent’s earliest effective filing date is January 12, 2018—i.e., its
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`actual filing date. Willey is a journal article published online by October-November
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`2014 [EX1003, ¶¶92-93; EX1031, 005], and thus qualifies as prior art under 35
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`U.S.C § 102(a)(1). Noven Pharma is an international patent application publication
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`that was filed on August 26, 1994 and published on March 7, 1996, and thus qualifies
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`as prior art under 35 U.S.C §§ 102(a)(1) and 102(a)(2). EX1005. Sotiriou is a journal
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`article published in the September 2009 edition of the Journal of the European
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`Academy of Dermatology and Venereology [EX1003, 186-187], and was publicly
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`available online by March 2011 [EX1031, 013], and thus qualifies as prior art under
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`35 U.S.C § 102(a)(1). Fautek is a journal article published online by February 2008
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`in the journal Archives of Dermatological Research, [EX1003, 287-288; EX1008,
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`53; EX1031, 009], and thus qualifies as prior art under 35 U.S.C § 102(a)(1).
`
`Ameluz® Prescribing Information was published on the Food and Drug
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`Administration Website by October 2016 [EX1003, 92-93; EX1031, 060-071], and
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`thus qualifies as prior art under 35 U.S.C § 102(a)(1). Likewise, the Blu-U Operating
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`Manual was published on PO’s website by at least 2006 [EX1003, 287-288;
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`EX1031, 072-089], and thus qualifies as prior art under 35 U.S.C § 102(a)(1).
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`Evidence of the public availability of Willey, Sotiriou, Fauteck, the Ameluz®
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`Prescribing Information and the BLU-U Operating Manual before January 12, 2018
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`is found in EX1031, which is an affidavit from the Internet Archive. EX1031.
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`Further evidence of public availability of Willey, Fauteck, and Sotiriou is found in
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`Exhibits 1032-1034.
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`Ground 1 asserts that the Challenged Claims are invalid based on published
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`descriptions of ALA photodynamic therapy treatments on the hands and forearms
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`using PO’s own marketed product—Levulan®—together with Saran Wrap—a
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`known low density polyethylene material used in the art. Ground 2 is not cumulative
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`with Ground 1 because it adds the Ameluz® prescribing information reference to
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`Ground 1, which addresses elements in claim 3 that PO may contend are not
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`inherently present. Ground 3 is not cumulative with Ground 1 because it adds the
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`use of red light as an illumination source to the disclosure in Ground 1, which is
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`focused on the application of blue light.
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`Ground 4 is not cumulative with Grounds 1-3 because Noven Pharma
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`specifically references the use of low density polyethylene as an occlusive material
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`for ALA photodynamic therapy treatments, to the extent that PO contends Willey’s
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`use of Saran Wrap is insufficient to disclose low density polyethylene. Ground 5 is
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`not cumulative with Ground 4 because it adds the Fauteck reference, which
`
`addresses elements in claim 3 that PO may contend are not inherently present.
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`Ground 6 is not cumulative with Ground 4 because it adds the BLU-U Operating
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`Manual reference, which addresses elements in claim 10 concerning the distance of
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`the light source from the treatment area.
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` Grounds 1-6 are also not cumulative with the art of record, including the art
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`of record expressly considered by the Examiner during prosecution of the ’567
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`Patent. During prosecution, the Examiner determined that the prior art of record does
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`not teach the claimed methods also including “removing the low density
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`polyethylene barrier applied to the treatment area prior to applying light to the
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`treatment area” and “wherein the treatment area is located on a hand or a forearm as
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`claimed.” EX1002, 015. Grounds 1-6 address these and other purported deficiencies
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`identified by the Examiner during prosecution.
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`Moreover, each of the asserted references is analogous art that is usable in an
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`obviousness combination. Unwired Planet, LLC v. Google Inc., 841 F.3d 995, 1000
`
`(Fed. Cir. 2016). Each reference is from the same field of endeavor as the ’567
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`patent, e.g., dermatological photodynamic therapy. EX1003, ¶33;¶90; In re Bigio,
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`381 F.3d 1320, 1325 (Fed. Cir. 2004). As analogous art, a person of ordinary skill
`
`in the art (POSITA) is presumed to have been aware of these references. In re
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`Nilssen, 851 F.2d 1401, 1403 (Fed. Cir. 1988).
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`V.
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`FIELD OF TECHNOLOGY
`The ’567 Patent states that “[t]he present disclosure relates generally to
`
`methods for photodynamic therapy.” EX1001, Abstract; Claims 1-10.
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`A.
`Photodynamic Therapy
`Topical photodynamic therapy (PDT) involves the administration of a
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`photosensitizing compound or a photosensitizer precursor compound to an area of
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`the skin to be treated, followed by exposure to light. EX1003, ¶36; EX1015, 5. The
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`photosensitizer is either absorbed directly into the skin when a photosensitizer
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`compound is applied, or may be generated within the cells being treated when a
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`photosensitizer precursor is applied. Id. Application of light to the photosensitized
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`cells results in the generation of singlet oxygen and free radicals. EX1003, ¶36;
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`EX1015, 5; EX1016, 52.
`
`
`EX1022, 4141-42. Singlet oxygen and free radicals are highly reactive, and can
`
`result in damage or death to the cells that they are present within. EX1003, ¶37;
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`EX1015, 5; EX1016, 52. Thus, if targeted to harmful cells like malignant cells,
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`photosensitizers and light (and the resulting generation of singlet oxygen and free
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`radicals) can be used for treatment. EX1003, ¶39; EX1015, 5-6.
`
`B.
`5-Aminolevulinic Acid (ALA)
`In the 1990s, scientists discovered that pre-cancerous and cancerous skin
`
`lesions could be treated and destroyed using a photosensitizer precursor known as
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`5-aminilevulinic acid (ALA), followed by administration of light. EX1003, ¶38;
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`EX1016, 52-54; EX1018, 221. When ALA is applied to skin lesions, pre-malignant
`
`and malignant cells selectively generate and accumulate more protoporphyrin IX
`
`(PpIX)—a photosensitizer—than normal cells. EX1003, ¶39; EX1016, 52; EX1018,
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`221. Because ALA causes pre-malignant and malignant cells to selectively
`
`accumulate PpIX, and because PpIX causes cell death under certain wavelengths of
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`light, ALA can be used to preferentially kill precancerous and cancerous cells while
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`leaving normal skin cells relatively unharmed. EX1003, ¶¶39-40; EX1016, 52;
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`EX1005, 1-2.
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`ALA is a non-proteinogenic amino acid that is present naturally in humans
`
`and used by the body in the heme biosynthesis pathway to help make hemoglobin—
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`a protein found in blood. EX1003, ¶38; EX100