111111111111111011111111111)gyl11111111111111111111111110111111
`
`(12) United States Patent
`Watanabe et al.
`
`(to) Patent No.: (cid:9)
`(45) Date of Patent: (cid:9)
`
`US 6,660,295 B2
`*Dec. 9, 2003
`
`TRANSDERMAL DRUG DELIVERY DEVICE
`PACKAGE WITH IMPROVED DRUG
`STABILITY
`
`Inventors: Tyler Watanabe, Los Altos, CA (US);
`Robert M. Gale, Los Altos, CA (US)
`
`Assignee: Alza Corporation, Mountain View, CA
`(US)
`
`Notice: (cid:9)
`
`This patent issued on a continued pros-
`ecution application filed under 37 CFR
`1.53(d), and is subject to the twenty year
`patent (cid:9)
`term (cid:9) provisions (cid:9) of 35 (cid:9) U.S.C.
`154(a)(2).
`
`Subject to any disclaimer, the term of this
`patent is extended or adjusted under 35
`U.S.C. 154(b) by 0 days.
`
`(21)
`(22)
`
`(65)
`
`Appl. No.: 09/162,534
`Filed: (cid:9)
`Sep. 29, 1998
`
`Prior Publication Data
`
`US 2001/0051180 Al Dec. 13, 2001
`
`4,201,211 A
`4,250,878 A
`4,274,420 A
`4,286,592 A
`4,299,719 A
`4,314,557 A
`3,598,122
`4,379,454 A
`4,435,180 A
`4,524,015 A
`4,559,222 A
`4,568,343 A
`4,588,580 A
`4,638,043 A
`4,640,689 A
`4,645,502 A
`4,698,062 A
`4,702,732 A
`4,704,282 A
`4,725,272 A
`4,747,845 A
`4,781,924 A
`4,784,857 A
`4,788,062 A
`4,816,258 A
`4,849,226 A
`4,904,475 A
`4,908,027 A
`4,917,895 A
`
`5/1980 Chandrasekaran et al. .. 128/268
`2/1981 Jacobsen et al. (cid:9)
` 128/207.21
`6/1981 Hymes (cid:9)
`
`128/641
`9/1981 Chandrasekaran (cid:9)
`
`128/260
`11/1981
`Aoki et al. (cid:9)
`
`252/188
`2/1982
`Chandrasekaran (cid:9)
`
`128/260
`11/1982
`Zaffaroni (cid:9)
`
`128/268
`4/1983 Campbell et al. (cid:9)
`
`604/897
`3/1984 Leeper (cid:9)
`
`604/896
`6/1985 Takahashi et al. (cid:9)
` 252/188.28
`12/1985 Enscore et al. (cid:9)
`
`424/28
`2/1986 Leeper et al. (cid:9)
`
`604/896
`5/1986 Gale et al. (cid:9)
`
`424/21
`1/1987 Szycher et al. (cid:9)
`
`528/75
`2/1987 Sibalis (cid:9)
`
`604/20
`2/1987 Gale et al. (cid:9)
`
`604/896
`10/1987 Gale et al. (cid:9)
`
`604/896
`10/1987 Powers et al. (cid:9)
`
`604/20
`11/1987
`Campbell et al. (cid:9)
`
`424/449
`2/1988
`Gale (cid:9)
`
`424/448
`5/1988 Korol (cid:9)
`
`604/368
`11/1988 Lee et al. (cid:9)
`
`424/449
`11/1988 Berry et al. (cid:9)
`
`424/449
`11/1988 Gale et al. (cid:9)
`
`424/449
`3/1989 Nedberge et al. (cid:9)
`
`424/448
`7/1989 Gale (cid:9)
`
`424/448
`2/1990 Gale et al. (cid:9)
`
`424/449
`3/1990 Enscore et al. (cid:9)
`
`604/890
`4/1990 Lee et al. (cid:9)
`
`424/448
`
`Related U.S. Application Data
`(60) Provisional application No. 60/060,397, filed on Sep. 30,
`1997.
`(51) Int. C1.7 (cid:9)
`(52) U.S. Cl. (cid:9)
`(58) Field of Search (cid:9)
`
` A61F 13/00
` 424/448; 424/449
` 424/448, 449
`
`(List continued on next page.)
`
`Primary Examiner—Shelley A. Dodson
`(74) Attorney, Agent, or Firm—Vandana Date
`
`(57)
`
`ABSTRACT
`
`(56)
`
`References Cited
`U.S. PATENT DOCUMENTS
`
`3,426,754 A (cid:9)
`3,598,123 A (cid:9)
`3,731,683 A (cid:9)
`3,797,494 A (cid:9)
`3,991,755 A (cid:9)
`4,031,894 A (cid:9)
`4,141,359 A (cid:9)
`
`2/1969 Bierenbaum et al. (cid:9)
`8/1971 Zaffaroni (cid:9)
`5/1973 Zaffaroni (cid:9)
`3/1974 Zaffaroni (cid:9)
`11/1976 Vernon et al. (cid:9)
`6/1977 Urquhart et al. (cid:9)
`2/1979 Jacobsen et al. (cid:9)
`
` 128/156
` 128/268
` 128/268
` 128/268
` 128/172.2
` 128/268
` 128/172.1
`
`This invention relates to the field of transdermal drug
`delivery devices and more particularly to improved storage
`stability thereof. The invention comprises providing a trans-
`dermal drug delivery device with a non-occlusive backing or
`release liner in combination with a degradation protectant
`such as a desiccant or oxygen scavenger within the sealed
`pouch containing the device. The combination of the present
`invention provides increased shelf-life of these devices.
`
`16 Claims, 1 Drawing Sheet
`
`NOVARTIS EXHIBIT 2025
`Noven v. Novartis and LTS Lohmann
`IPR2014-00550
`Page 1 of 6
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`

`US 6,660,295 B2
`Page 2
`
`U.S. PATENT DOCUMENTS
`
`4,928,680 A (cid:9)
`4,938,759 A (cid:9)
`4,943,435 A (cid:9)
`4,992,410 A (cid:9)
`4,994,278 A (cid:9)
`5,004,610 A (cid:9)
`5,071,656 A (cid:9)
`5,077,104 A (cid:9)
`5,141,750 A (cid:9)
`5,143,769 A (cid:9)
`5,207,943 A (cid:9)
`5,208,431 A (cid:9)
`5,223,261 A (cid:9)
`5,242,433 A (cid:9)
`
`5/1990 (cid:9) Sandbank (cid:9)
`7/1990 (cid:9) Enscore et al. (cid:9)
`7/1990 (cid:9) Baker et al. (cid:9)
`2/1991 (cid:9) Cullen et al. (cid:9)
`2/1991 (cid:9) Sablotsky et al. (cid:9)
`4/1991 (cid:9) Osborne et al. (cid:9)
`12/1991 (cid:9) Lee et al. (cid:9)
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`9/1993 (cid:9) Smith et al. (cid:9)
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`128/155
`604/896.1
`424/448
`502/407
`424/449
`424/448
`424/448
`428/34.3
`424/448
`428/76
`252/188.28
`219/121.65
`424/443
`604/289
`
`5,258,179 A
`5,262,375 A
`5,268,209 A
`5,332,590 A
`5,342,623 A
`5,352,456 A
`5,362,501 A
`5,364,555 A
`5,411,740 A
`5,411,750 A
`5,500,222 A
`5,536,263 A
`5,614,211 A
`5,635,203 A
`5,698,217 A
`
`11/1993 (cid:9) Bracco et al. (cid:9)
`11/1993 McKedy (cid:9)
`12/1993 (cid:9) Hunt et al. (cid:9)
`7/1994 McKedy (cid:9)
`8/1994 (cid:9) Enscore et al. (cid:9)
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`11/1994 (cid:9) Gopeland et al. (cid:9)
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`3/1996 (cid:9) Lee et al. (cid:9)
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`3/1997 (cid:9) Gale et al. (cid:9)
`6/1997 (cid:9) Gale et al. (cid:9)
`12/1997 Wilking (cid:9)
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`424/94.1
`502/406
`428/34.4
`426/398
`424/448
`424/448
`426/12
`252/188.28
`424/448
`424/717
`424/448
`604/307
`424/448
`424/448
`424/448
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`NOVARTIS EXHIBIT 2025
`Noven v. Novartis and LTS Lohmann
`IPR2014-00550
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`

`

`U.S. Patent (cid:9)
`
`Dec. 9, 2003 (cid:9)
`
`US 6,660,295 B2
`
`4-
`
`FIG. 1
`
`NOVARTIS EXHIBIT 2025
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`

`1
`TRANSDERMAL DRUG DELIVERY DEVICE
`PACKAGE WITH IMPROVED DRUG
`STABILITY
`
`This is a provisional of application No. 60/060,397 filed 5
`on Sep. 30, 1997.
`
`FIELD OF THE INVENTION
`
`This invention relates to transdermal drug delivery
`devices and more particularly, to a method for protecting
`such devices from degradation such as that due to hydrolysis
`and/or oxidation during storage.
`
`BACKGROUND OF THE INVENTION
`
`The transdermal route of parenteral drug delivery pro-
`vides many advantages over other administrative routes.
`Transdermal drug delivery devices, including multilami-
`nates and monoliths, for delivering a wide variety of drugs
`or other beneficial agents are described in U.S. Pat. Nos.
`3,598,122; 3,598,123; 3,731,683; 3,797,494; 4,031,894;
`4,201,211; 4,286,592; 4,314,557; 4,379,454; 4,435,180;
`4,559,222; 4,568,343; 4,588,580; 4,645,502; 4,698,062;
`4,704,282; 4,725,272; 4,781,924; 4,788,062; 4,816,258;
`4,849,226; 4,904,475; 4,908,027; 4,917,895; 4,938,759;
`4,943,435; 5,004,610; 5,071,656; 5,141,750; 5,342,623;
`5,411,740; and 5,635,203, all of which are hereby incorpo-
`rated in their entirety by reference.
`Drugs may also be administered transdermally by
`iontophoresis, and iontophoretic delivery devices for deliv-
`ering a wide variety of drugs of other beneficial agents are
`well known in the art. Iontophoretic devices include a donor
`electrode assembly which includes a donor electrode and a
`reservoir containing the beneficial agent to be iontophoreti-
`cally delivered. The device also includes a counter electrode
`assembly and an electric power source. Typical devices are
`disclosed in U.S. Pat. Nos. 3,991,755, 4,141,359, 4,250,878,
`4,274,420, 4,640,689, and 4,702,732, for example, all of
`which are incorporated herein by reference.
`One problem associated with the devices of the prior art
`is degradation of the contents of the device, such as the
`drugs, permeation enhancers, matrix materials, or other
`components contained therein. Degradation not only unde-
`sirably breaks down these materials, but it also causes
`discoloration and formation of odors within the pouched
`system. Devices susceptible to degradation can not be stored
`for a reasonable amount of time, thus causing practical
`problems in their distribution.
`A solution disclosed in the prior art is to incorporate an
`antioxidant into the device. For example, U.S. Pat. Nos.
`5,028,431 and 5,242,433, hereby incorporated in their
`entirety by reference, disclose mixing antioxidants such as
`BHT into the drug formulation of a transdermal drug deliv-
`ery device due to the unstable nature of the drug to be
`delivered.
`Another solution has been to incorporate a desiccant
`material within the sealed pouch containing the transdermal
`drug delivery device. For example, the Climara® transder-
`mal estradiol system is packaged and sold within a sealed
`pouch containing a water scavenger to protect against
`hydrolysis of estradiol. This system is disclosed in U.S. Pat.
`No. 5,223,261 and the dessicant containing package is
`disclosed in U.S. Pat. No. 5,698,217, which are hereby
`incorporated in their entirety by reference.
`Transdermal drug delivery systems typically comprise at
`a minimum a drug reservoir layer covered or surrounded by
`
`10
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`US 6,660,295 B2
`
`2
`a backing layer and a release liner. The backing layer may
`be occlusive or non-occlusive. For example, the Climara®
`system comprises a polyethylene backing layer having a low
`moisture vapor transmission rate (MVTR) of approximately
`7-11 g/m2. 24 hr. More open backing layers such as spun
`laced polyester (Sontara®) are disclosed in U.S. Pat. Nos.
`5,411,750, 5,500,222, and 5,614,211, which are incorpo-
`rated herein by reference. Other non-occlusive backing
`layers are disclosed in U.S. Pat. Nos. 3,426,754, 4,638,043,
`4,994,278, 5,352,456, and 5,536,263, all of which are
`hereby incorporated in their entirety by reference.
`We have found that even when placed in pouches con-
`taining degradation protectants such as antioxidants and
`desiccants, certain transdermal delivery devices still degrade
`at rates higher than desirable. Thus, there is a need for
`improved storage stability of such devices.
`
`DEFINITION OF TERMS
`
`As used herein, the term "degradation" refers to any
`change in any of the device components during storage, for
`example by hydrolysis and/or oxidation of the drug, perme-
`ation enhancers, matrix materials, and any other excipients
`contained within the device.
`As used herein, the term "degradation agent" refers to any
`agent within the device or pouch which causes an undesir-
`able by-product, such as water and/or oxidizing agents.
`As used herein, the term "degradation protectant" refers to
`any material which protects against degradation of any of
`the device components such as water scavengers, oxygen
`scavengers, or combinations thereof.
`As used herein, the term "non-occlusive" refers to a
`material having a moisture vapor transmission rate (MVTR)
`of not less than 20 g/m2.24 hr.
`
`SUMMARY OF THE INVENTION
`
`We have found that many transdermal drug delivery
`devices contain degradation agents that must be removed or
`scavenged from the device in order to maintain stability.
`When impermeable backings are used, the only pathway
`which these materials can be exposed to the degradation
`protectant is through the unsealed edges of the device.
`Diffusion through this pathway is very slow.
`According to our invention, we have found that stability
`of such devices can be considerably improved when stored
`in pouches containing degradation protectants if the trans-
`dermal device uses a non-occlusive backing.
`Accordingly, it is an aspect of this invention to provide an
`improved method for preventing degradation of the compo-
`nents of transdermal drug delivery devices.
`It is another aspect of this invention to provide an
`improved packaged transdermal drug delivery device com-
`prising a transdermal drug delivery device having a non-
`occlusive backing layer contained within a sealed pouch
`containing a degradation protectant.
`It is another aspect to increase the shelf-life of a trans-
`dermal drug delivery device.
`It is yet another aspect of this invention to provide
`improved packaged oxybutynin transdermal drug delivery
`systems.
`The present invention comprises a combination of a
`transdermal drug delivery device having a non-occlusive
`backing layer wherein the device is sealed within a pouch
`containing a degradation protectant. The combination of the
`non-occlusive backing layer and the degradation protectant
`
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`US 6,660,295 B2
`
`3
`within the sealed pouch protects the contents of the trans-
`dermal drug delivery device from degradation.
`
`BRIEF DESCRIPTION OF THE DRAWINGS
`
`FIG. 1 depicts a cross-sectional view of one embodiment
`of this invention.
`
`5
`
`DETAILED DESCRIPTION OF THE
`INVENTION
`
`4
`The combination device and package of the present
`invention protects against degradation of any of the com-
`ponents of the transdermal drug delivery device, such as the
`drug, permeation enhancers, and any potential by-products.
`For example, esters can undergo acid or base catalyzed
`hydrolysis and/or trans-esterification which result in the
`formation of breakdown products of the corresponding acid
`and alcohol. Practice of this invention is not to be limited to
`any particular drug, permeation enhancer, or other excipient.
`However, devices containing labile ester drugs and perme-
`ation enhancers, such as fatty acid esters, are particularly
`suited for practice of this invention.
`Examples of drugs include estradiol, fluoxetine,
`paroxetine, and ester drugs such as oxybutynin.
`Examples of permeation enhancers include monoglycer-
`ides or mixtures of monoglycerides of fatty acids having a
`total monoesters content of at least 51% wherein the
`monoesters are those with from 10-20 carbon atoms such as
`glycerol monolaurate, glycerol monooleate, and glycerol
`monolinoleate, fatty acids and esters of fatty acids having
`from about 10 to about 20 carbon atoms, polyethylene glycol
`monolaurate, and combinations thereof. Fatty acids are, for
`example, lauric acid, myristic acid, stearic acid, oleic acid,
`linoleic acid, and palmitic acid and fatty acid esters include,
`for example, lauryl lactate, isopropyl myristate, dodecyl
`acetate, ethyl palmitate, and methyl laurate.
`The degradation protectants for use with the present
`invention are known in the art. Suitable degradation pro-
`tectants are disclosed in, for example and not by way of
`limitation, U.S. Pat. Nos. 4,299,719, 4,524,015, 4,992,410,
`5,143,769, 5,207,943, 5,258,179, 5,262,375 5,332,590,
`5,362,501, and 5,364,555, which are hereby incorporated in
`their entirety by reference. Preferred water scavengers
`include anhydrous calcium sulfate such as Drierite®, anhy-
`drous silica gel powders such as NatrasorbTM, and Desi-
`max® produced by Multiform Technologies. A preferred
`water and oxygen scavenger is FreshpaxTM produced by
`Multiform Technologies. The amount of degradation pro-
`tectant required depends on the volume of the protected
`space and the expected water content of the drug delivery
`device, with sufficient overcapacity, and may readily be
`determined by one of ordinary skill.
`The pouch material is selected from materials known in
`the art. It is preferred that that pouch material is self-sealable
`and acts as a barrier to the drug contained within the device.
`For example, suitable pouch materials are disclosed in U.S.
`Pat. Nos. 5,077,104 and 5,268,209, which are hereby incor-
`porated in their entirety by reference.
`A preferred embodiment is directed to transdermal drug
`delivery devices for administering oxybutynin. Such devices
`are disclosed in U.S. Pat. Nos. 5,411,750, 5,500,222, and
`5,614,211, listed above, and are also disclosed in U.S. Pat.
`Nos. 4,747,845, 4,784,857, and 4,928,680, which are hereby
`incorporated in their entirety by reference. The present
`inventors have found that oxybutynin within such systems
`breaks down to oxybutynin-N-oxide, a yellowish
`by-product. According to this preferred embodiment, a deg-
`radation protectant which is both a water and oxygen
`scavenger is sealed within the pouch. The backing is pref-
`erably spun-laced polyester such as Sontara® manufactured
`by DuPont of Wilmington, Del.
`Although the invention has been described with respect to
`the use of a non-occlusive backing, a non-occlusive release
`liner could also be used in those cases where the use of the
`device may require an occlusive backing.
`The aforementioned patents describe a wide variety of
`materials for fabricating the various layers or components of
`
`10
`
`15
`
`According to the present invention, an improved pack-
`aged transdermal drug delivery device and method for
`preventing degradation thereof are provided. The improve-
`ment comprises providing a transdermal drug delivery
`device with a non-occlusive backing in combination with
`incorporating a degradation protectant into the pouch con-
`taining the device. The resultant combination provides
`improved protection against degradation of the contents of
`the delivery device, thereby increasing the shelf-life of such
`devices.
`With reference to FIG. 1, the packaged transdermal drug
`delivery device 10 includes backing layer 1, drug reservoir
`layer 2, and release liner 3 which make up the drug delivery
`device. The device is packaged within pouch 5 which also
`includes degradation protectant 4. Alternately, the device
`may include additional layers such as a rate control mem-
`brane (not shown) or in-line contact adhesive (not shown) as
`known in the art.
`The porosity of the backing layer must be sufficient to
`allow the degradation agents and products within the deliv-
`ery device to readily diffuse through the backing layer. This
`is necessary to enable the degradation agents and products
`located at or near the center of the device to diffuse through
`the system backing to be absorbed by the degradation
`protectant. If the backing layer is too occlusive, the only
`available path for diffusion of the degradation agents con-
`tained within the device is through the system edges. This
`may not be sufficient to allow all the degradation agents
`products located at or near the center of the device to diffuse
`through the system to be absorbed by the degradation
`protectant.
`The non-occlusive backings of the present invention
`comprise a MVTR of greater than about 20 g/m2.24 hr and
`are preferably within the range of human skin of about
`70-150 g/m2.24 hr. Backings having a MVTR within the
`range of human skin are preferred as they also result in
`enhanced adhesion of some devices, particularly those com-
`prising surfactant-like permeation enhancers. Backings with
`a higher MVTR can also be utilized in accordance with the
`present invention.
`Suitable backing layer materials include woven or non-
`woven materials. For example and not by way of limitation,
`non-woven materials include spun-laced or spun-bonded
`polyester, polyethylene or polypropylene and the like,
`microporous or macroporous polyester, polypropylene, or 55
`polyethylene and the like, rayon, polyester/rayon, and
`polypropylene/rayon. Woven materials include, for
`example, cloth, nylon and nylon/rayon taffeta.
`According to another embodiment of this invention, the
`desired porosity of the backing layer may be derived by 60
`piercing the backing layer with a predetermined number of
`holes. This may be done, for example, by firmly applying a
`backing layer against a substrate comprising an array of
`piercing elements. The array of piercing elements may be
`selected to provide the desired porosity. According to this 65
`embodiment, backing layers which are otherwise too occlu-
`sive may be rendered suitable for practice of this invention.
`
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`5
`transdermal drug delivery devices for use according to this
`invention. This invention therefore contemplates the use of
`materials other than those specifically disclosed herein,
`including those which may hereafter become known to the
`art to be capable of performing the necessary functions. The
`following example is intended to illustrate the practice of
`this invention and is not intended to limit the invention in
`any manner.
`
`EXAMPLE 1
`
`An oxybutynin/permeation enhancer reservoir is prepared
`by mixing ethylene vinyl acetate copolymer having a vinyl
`acetate content of 40 percent in an internal mixer (Brabender
`type mixer) until the EVA 40 pellets are fused. Oxybutynin,
`glycerol monolaurate, and a fatty acid ester cosolvent such
`as dodecyl acetate are then added. The mixture is blended,
`cooled and calendered to a 5 mil thick film.
`The drug reservoir film is then laminated to a spun-laced
`polyester backing layer such as a Sontara® backing
`(DuPont, Wilmington, Del.) on its skin distal surface and a
`Celgard microporous polypropylene membrane tie layer on
`its skin facing surface. A contact adhesive is then laminated
`to the microporous polypropylene tie layer and an imper-
`meable release liner is laminated to the contact adhesive.
`A packet containing degradation protectant such as Fresh-
`pax TM (Multiform Technologies, Buffalo, N.Y.) is adhered to
`the inside of a pouch. The multilaminate device is then
`placed within the pouch and the pouch is sealed, for
`example, by heat sealing.
`This invention has been described in detail with particular
`reference to certain preferred embodiments thereof, but it
`will be understood that variations and modifications can be
`effected within the spirit and scope of this invention.
`What is claimed is:
`1. A package for a transdermal drug delivery device
`comprising, in combination:
`a pouch containing:
`(a) a transdermal drug delivery device comprising a
`drug reservoir layer positioned between a release
`liner and a backing layer, at least one of said release
`liner and said backing layer being non-occlusive;
`(b) a degradation protectant.
`2. The combination of claim 1 wherein the non-occlusive
`layer comprises a moisture vapor transmission rate of at
`least 30 g/m2.24 hr.
`3. The combination of claim 1 wherein the non-occlusive
`layer comprises a moisture vapor transmission rate of about
`70-150 g/m2.24 hr.
`
`25 (cid:9)
`
`3 0
`
`40 (cid:9)
`
`US 6,660,295 B2
`
`15 (cid:9)
`
`6
`4. The combination of claim 1 wherein the drug reservoir
`comprises drug dispersed within an adhesive layer.
`5. The combination of claim 1 further comprising a
`contact adhesive layer between the drug reservoir and the
`5 release liner.
`6. The combination of claim 1 wherein the degradation
`protectant is a water scavenger.
`7. The combination of claim 1 wherein the degradation
`protectant is an oxygen scavenger.
`10 8. The combination of claim 1 wherein the degradation
`protectant comprises a water scavenger and an oxygen
`scavenger.
`9. The combination of claim 1 wherein the drug reservoir
`comprises oxybutynin.
`10. The combination of claim 9 wherein the backing layer
`comprises spun-laced polyester.
`11. The combination of claim 10 wherein the degradation
`protectant comprises an oxygen scavenger.
`12. The combination of claim 11 wherein the degradation
`20 protectant additionally scavenges water.
`13. A method for preventing degradation of a transdermal
`drug delivery device of the type comprising a drug reservoir
`positioned between a backing layer and a release liner
`comprising:
`(a) providing the transdermal drug delivery device with a
`non-occlusive backing layer or release liner comprising
`a moisture vapor transmission rate of at least 20
`g/m2.24 hr;
`(b) placing a degradation protectant within a pouch;
`(c) placing the device within the pouch;
`(d) sealing the pouch.
`14. A method for increasing the shelf-life of a transdermal
`drug delivery device of the type comprising a drug reservoir
`35 positioned between a backing layer and a release liner
`comprising:
`(a) providing the transdermal drug delivery device with a
`non-occlusive backing layer or release liner comprising
`a moisture vapor transmission rate of at least 20
`g/m2.24 hr r;
`(b) placing a degradation protectant within a pouch;
`(c) placing the device within the pouch;
`(d) sealing the pouch.
`15. The package of claim 1 wherein said transdermal drug
`45 delivery device contains at least one degradation agent.
`16. The method of claim 14 wherein said transdermal
`drug delivery device contains at least one degradation agent.
`
`NOVARTIS EXHIBIT 2025
`Noven v. Novartis and LTS Lohmann
`IPR2014-00550
`Page 6 of 6
`
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