~ttorney's Docket No. 1199-26
`-...1 __..
`CJ.:)
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`PATENT
`
`c:::
`~ail Stop: PATENT APPLICATION
`_£ommissioner for Patents
`CJt-'.0. Box 1450
`Alexandria, VA 22313-1450
`
`NONPROVISIONAL PATENT APPLICATION TRANSMITTAL
`
`Sir:
`
`Transmitted herewith for filing is the patent application of:
`
`First Named Inventor (or Inventors):
`
`~
`
`YANG, Robert K., a citizen of the United States of America
`138-10 Franklin Avenue, apt. #2C, Flushing, NY 11355
`FUISZ, Richard C., a citizen of the United States of America
`1287 Ballantrae Farm Drive, Mclean, VA 22101
`MYERS, Gary L., a citizen of the United States of America
`908 Colfax Avenue, Kingsport, TN 37660
`FUISZ, Joseph M., a citizen of the United States of America
`5700 Cricket Place, Mclean, VA 221 01
`
`Title of Application:
`
`POLYETHYLENE OXIDE-BASED FILMS AND DRUG DELIVERY SYSTEMS
`MADE THEREFROM
`
`1.
`
`Type of Application (37 C.F.R. 1.53(b))
`
`This application is a(n):
`
`1:8]
`D
`
`Original (nonprovisional) application.
`
`Continuing application:
`D Divisional
`D Continuation
`of Serial No. __ , filed on __ .
`
`D Continuation-in-Part (CIP)
`
`CERTIFICATION UNDER 37 C.F.R. 1.10
`
`I hereby certify that this New Application Transmittal and the documents referred to as enclosed herein are being
`deposited with the United States Postal Service on this date, May 28. 2004, in an envelope as "Express Mail to
`Addressee" Mailing Label Number EV481312673US, addressed to Mail Stop: Patent Application, Commissioner of
`Patents, P.O. Box 1450, Alexandria, VA 22313-1450.
`
`Barbara Thomas
`Name of person mailing paper
`
`(Application Transmittal Page 1 of 6)
`
`RBP_TEVA05018708
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`DRL - EXHIBIT 1017
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`

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`2.
`
`Benefit of Prior U.S. Application(s) (35 U.S.C. 119(e), 120, or 121)
`
`1:8]
`
`D
`
`This new application claims the benefit of prior U.S. application(s).
`
`A Preliminary Amendment is enclosed amending this application to state the
`relation of this application to prior applications.
`
`The relation of this application to prior applications is stated in the application.
`
`3.
`
`35 U.S.C. 119(a)-(d) or 35 U.S.C. 365(a)-(b) Foreign Priority Claim for Prior
`Application
`
`This application, and prior U.S. application(s), including any prior International
`Application designating the U.S., identified above in item 2, claim(s) priority from one or
`more foreign applications as follows:
`
`(Country)
`
`(Application No.)
`
`(Filing Date)
`(mm/ddlyyyy)
`
`Certified copy(ies) of the application(s) from which priority under 35 U.S.C. 119 is
`claimed:
`
`D
`D
`D
`
`has(have) been filed on __ , in prior application __ , which was filed
`on __
`is (are) enclosed.
`willfollow.
`
`(Application Transmittal Page 2 of 6)
`
`RBP_TEVA05018709
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`DRL - EXHIBIT 1017
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`4.
`
`Enclosed Papers Required to Obtain Application Filing Date under 37 C.F.R.
`1.53(b)
`
`~ Pages of Specification
`__ 5 Pages of Claims
`__ 1 Pages of Abstract
`_.;:;,34..:.. Sheets of Drawings
`
`D Formal
`
`[8] Informal
`
`5.
`
`Oath or Declaration
`D
`D
`
`Newly executed Oath or Declaration (original or copy) is enclosed.
`
`Copy of Oath or Declaration from prior continuation or divisional application
`__ (37 C.F.R. 1.63(d)).
`
`D
`
`The entire disclosure of the prior application, from which a copy of the
`oath or Declaration is supplied, is considered as being a part of the
`disclosure of the accompanying application and is hereby incorporated by
`reference therein.
`
`A Power of Attorney is included in the Oath or Declaration.
`
`Not enclosed.
`
`D
`
`[8]
`
`6.
`
`Additional Papers Enclosed
`
`[8]
`D
`D
`D
`
`D
`
`D
`D
`D
`
`Return Receipt Postcard (specifically itemized) (M.P.E.P. § 503).
`
`Application Data Sheet (Voluntary under 37 C.F.R. 1.76).
`
`Preliminary Amendment.
`
`Information Disclosure Statement (37 C.F.R. 1.98).
`
`D
`
`Form PT0-1449
`
`D
`
`Copies of IDS Citations
`
`Nucleotide and/or Amino Acid Sequence Listing computer-readable copy, paper
`copy, and statement verifying identity of computer-readable and paper copies.
`
`Certified Copy of Priority Document(s).
`
`Verified translation of non-English language application (37 C.F.R. 1.52(d)).
`
`Other: __
`
`(Application Transmittal Page 3 of 6)
`
`RBP_TEVA05018710
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`7.
`
`Assignment
`
`~ An assignment of the invention to MonoSoiRx LLC.
`D
`
`is enclosed. A separate:
`D
`
`"Cover Sheet for Assignment (Document) Accompanying New
`Patent Application" is enclosed.
`
`D
`
`Form PT0-1595 is enclosed.
`
`D
`
`was made in prior application No. __ , filed on __ .
`
`D
`
`A copy of the assignment (and any recordation cover sheet) is
`enclosed.
`
`will follow.
`
`Not enclosed.
`
`8.
`
`Request That Application Not Be Published Pursuant to 35 U.S.C. 122(b)(2)
`D
`
`Pursuant to 35 U.S.C. 122(b)(2), Applicant(s) hereby requests that this
`patent application not be published pursuant to 35 U.S.C. 122(b)(1 ).
`Applicant hereby certifies that the invention disclosed in this application
`has not and will not be the subject of an application filed in another
`country, or under a multilateral international agreement, that requires
`publication of applications 18 months after filing of the application.
`
`Warning
`
`An applicant who makes a request not to publish, but who subsequently files in a
`foreign country or under a multilateral international agreement specified in 35
`U.S. C. 122(b)(2)(B)(i), must notify the Director of such filing not later than 45 days
`after the date of the filing of such foreign or international application. A failure of
`the applicant to provide such notice within the prescribed period shall result in
`the application being regarded as abandoned, unless it is shown to the
`satisfaction of the Director that the delay in submitting the notice was
`unintentional.
`
`(Application Transmittal Page 4 of 6)
`
`RBP_TEVA05018711
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`9.
`
`Fee Calculation (37 C.F.R. 1.16)
`
`Utility Application (37 C.F.R. 1.16(a))
`
`Basic Fee
`
`$770.00
`
`FEES FOR CLAIMS AS FILED
`
`Number filed
`
`Number extra
`
`Rate
`
`Total Claims
`(37 C.F.R. 1.16 (c))
`
`36
`
`- 20
`
`Independent Claims
`(37 C.F.R. 1.16(b))
`
`10
`
`- 3
`
`Multiple Dependent Claims
`(37 C.F.R. 1.16(d))
`
`= 16
`
`= 7
`
`X $ 18.00
`
`X $86.00
`
`=
`
`=
`
`$288.00
`
`$602.00
`
`+ $290.00
`
`=
`Fee Calculation for Extra Claims
`
`$0.00
`
`$890.00
`
`D
`D
`
`Amendment canceling extra claims enclosed.
`
`Amendment deleting multiple-dependencies enclosed.
`
`Total Filing Fee Calculation
`
`$1.660.00
`
`1 0.
`
`Small Entity Statement
`D
`
`Small entity status is claimed under 37 C.F.R. 1.27.
`
`Filing Fee Calculation (50% of Filing Fee calculated in Item 9 above)
`
`$ __
`
`11.
`
`Fee Payment
`D
`
`Not enclosed. No filing fee is to be paid at this time.
`
`[8]
`
`Enclosed:
`
`Basic filing fee (Item 9 or 10 above)
`
`$1.660.00
`
`Fee for recording Assignment
`$40.00 (37 C.F.R. 1.21(h))
`
`0
`
`Processing and retention fee
`$130.00 (37 C.F.R. 1.53(d) and 1.21(1))
`
`Total fees enclosed
`
`$ __
`
`$ __
`
`$1.660.00.
`
`(Application Transmittal Page 5 of 6)
`
`RBP_TEVA05018712
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`12. Method of Payment of Fees
`
`~ Check in the amount of $1 ,660.00.
`D
`
`Charge Deposit Account No. __ in the amount of $ __
`A duplicate of this transmittal is enclosed.
`
`13.
`
`Authorization to Charge Additional Fees
`
`~ The Commissioner is hereby authorized to charge the following additional fees
`by this paper and during the entire pendency of this application to Deposit
`Account No. 08-2461:
`
`~ 37 C.F.R. 1.16(a}, (f), or (g) (filing fees)
`
`~ 37 C.F.R. 1.16(b}, (c), and (d) (presentation of extra claims)
`
`~ 37 C.F.R. 1.16(e) (surcharge for filing the basic fee and/or declaration at
`a date later than the filing date of the application)
`
`D
`
`37 C.F.R. 1.17 (application processing fees)
`
`A duplicate of this transmittal is enclosed.
`
`14.
`
`Instructions as to Overpayment
`
`~ Credit Deposit Account 08-2461.
`
`D Refund.
`
`15.
`
`Correspondence Address
`
`Customer Number or Bar Code Label:
`
`23869
`
`Ja{jij;;.~
`
`Registration No. 48,623
`Attorney/Agent for Applicant(s)
`
`(Application Transmittal Page 6 of 6)
`
`RBP_TEVA05018713
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`

`
`1199-26
`
`PATENT
`
`POLYETHYLENE OXIDE-BASED FILMS AND DRUG
`DELIVERY SYSTEMS MADE THEREFROM
`
`CROSS-REFERENCE TO RELATED APPLICATIONS
`
`[0001]
`
`This application claims the benefit of U.S. Provisional Application No.
`
`60/473,902, filed May 28, 2003 and is a continuation-in-part ofPCT/US02/32575 filed October
`
`11, 2002, which claims priority to U.S. Application No. 10/074,272, filed February 14, 2002
`
`which claims priority to U.S. Provisional Application No. 60/328,868, filed October 12, 2001
`
`and U.S. Provisional Application No. 60/386,937, filed June 7, 2002; PCT/US02/32594, filed
`
`October 11, 2002, which claims priority to U.S. Provisional Application No. 60/414,276, filed
`
`September 27, 2002, U.S. Application No. 10/074,272, filed February 14, 2002, which claims
`
`priority to U.S. Provisional Application No. 60/328,868, filed October 12, 2001 and U.S.
`
`Provisional Application No. 60/386,937, filed June 7, 2002; and PCT/US02/32542, filed October
`
`11, 2002, which claims priority to U.S. Provisional Application No. 60/371,940, filed April11,
`
`2002, U.S. Application No. 10/074,272, filed February 14,2002, which claims priority to U.S.
`
`Provisional Application No. 60/328,868, filed October 12,2001 and U.S. Provisional
`
`Application No. 60/386,937, filed June 7, 2002.
`
`FIELD OF THE INVENTION
`
`[0002]
`
`The invention relates to rapidly dissolving films and methods of their preparation.
`
`The films contain a polymer component, which includes polyethylene oxide optionally blended
`
`with cellulosic polymers. The films may also contain an active ingredient that is evenly
`
`distributed throughout the film. The even or· uniform distribution is achieved by controlling one
`
`or more parameters, and particularly the elimination of air pockets prior to and during film
`
`formation and the use of a drying process that reduces aggregation or conglomeration of the
`
`components in the film as it forms into a solid structure.
`
`BACKGROUND OF THE RELATED TECHNOLOGY
`
`[0003]
`
`Active ingredients, such as drugs or pharmaceuticals, may be prepared in a tablet
`
`form to allow for accurate and consistent dosing. However, this form of preparing and
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`RBP_TEVA05018714
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`DRL - EXHIBIT 1017
`DRL007
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`

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`. '·'
`'
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`dispensing medications has many disadvantages including that a large proportion of adjuvants
`
`that must be added to obtain a size able to be handled, that a larger medication form requires
`
`additional storage space, and that dispensing includes counting the tablets which has a tendency
`
`for inaccuracy. In addition, many persons, estimated to be as much as 28% of the population,
`
`have difficulty swallowing tablets. While tablets may be broken into smaller pieces or even
`
`crushed as a means of overcoming swallowing difficulties, this is not a suitable solution for
`
`many tablet or pill forms. For example, crushing or destroying the tablet or pill form to facilitate
`
`ingestion, alone or in admixture with food, may also destroy the controlled release properties.
`
`[0004]
`As an alternative to tablets and pills, films may be used to carry active ingredients
`such as drugs, pharmaceuticals, and the like. However, historically films and the process of
`
`making drug delivery systems therefrom have suffered from a number of unfavorable
`
`characteristics that have not allowed them to be used in practice.
`
`[0005]
`
`Films that incorporate a pharmaceutically active ingredient are disclosed in
`
`expired U.S. Patent No. 4,136,145 to Fuchs, et al. ("Fuchs"). These films may be formed into a
`
`sheet, dried and then cut into individual doses. The Fuchs disclosure alleges the fabrication of a
`
`uniform film, which includes the combination of water-soluble polymers, surfactants, flavors,
`sweeteners, plasticizers and drugs. These allegedly flexible films are disclosed as being useful
`
`for oral, topical or enteral use. Examples of specific uses disclosed by Fuchs include application
`
`of the films to mucosal membrane areas of the body, including the mouth, rectal, vaginal, nasal
`
`and ear areas.
`
`[0006]
`
`Examination of films made in accordance with the process disclosed in Fuchs,
`
`however, reveals that such films suffer from the aggregation or conglomeration of particles, i.e.,
`
`self-aggregation, making them inherently non-uniform. This result can be attributed to Fuchs'
`
`process parameters, which although not disclosed likely include the use of relatively long drying
`
`times, thereby facilitating intermolecular attractive forces, convection forces, air flow and the
`
`like to form such agglomeration.
`
`2
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`RBP_TEVA05018715
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`[0007]
`
`The formation of agglomerates randomly distributes the film components and any
`
`active present as well. When large dosages are involved, a small change in the dimensions of the
`
`film would lead to a large difference in the amount of active per film. If such films were to
`
`include low dosages of active, it is possible that portions of the film may be substantially devoid
`
`of any active. Since sheets of film are usually cut into unit doses, certain doses may therefore be
`
`devoid of or contain an insufficient amount of active for the recommended treatment. Failure to
`
`achieve a high degree of accuracy with respect to the amount of active ingredient in the cut film
`
`can be harmful to the patient. For this reason, dosage forms formed by processes such as Fuchs,
`
`would not likely meet the stringent standards of governmental or regulatory agencies, such as the
`
`U.S. Federal Drug Administration ("FDA"), relating to the variation of active in dosage forms.
`
`Currently, as required by various world regulatory authorities, dosage forms may not vary more
`
`than 10% in the amount of active present. When applied to dosage units based on films, this
`
`virtually mandates that uniformity in the film be present.
`
`[0008]
`
`The problems of self-aggregation leading to non-uniformity of a film were
`
`addressed in U.S. Patent No. 4,849,246 to Schmidt ("Schmidt"). Schmidt specifically pointed
`
`out that the methods disclosed by Fuchs did not provide a uniform film and recognized that that
`
`the creation of a non-uniform film necessarily prevents accurate dosing, which as discussed
`
`above is especially important in the pharmaceutical area. Schmidt abandoned the idea that a
`
`mono-layer film, such as described by Fuchs, may provide an accurate dosage form and instead
`
`attempted to solve this problem by forming a multi-layered film. Moreover, his process is a
`
`multi-step process that adds expense and complexity and is not practical for commercial use.
`
`[0009]
`
`Other U.S. Patents directly addressed the problems of particle self-aggregation
`
`and non-uniformity inherent in conventional film forming techniques. In one attempt to
`
`overcome non-uniformity, U.S. Patent 5,629,003 to Horstmann et al. and U.S. Patent 5,948,430
`
`to Zerbe et al. incorporated additional ingredients, i.e. gel formers and polyhydric alcohols
`
`respectively, to increase the viscosity of the film prior to drying in an effort to reduce
`
`aggregation of the components in the film. These methods have the disadvantage of requiring
`
`additional components, which translates to additional cost and manufacturing steps.
`
`Furthermore, both methods employ the use the conventional time-consuming drying methods
`
`3
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`RBP_TEVA05018716
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`.t
`
`_;
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`such as a high-temperature air-bath using a drying oven, drying tunnel, vacuum drier, or other
`
`such drying equipment. The long length of drying time aids in promoting the aggregation of the
`
`active and other adjuvant, notwithstanding the use of viscosity modifiers. Such processes also
`
`run the risk of exposing the active, i.e., a drug, or vitamin C, or other components to prolonged
`
`exposure to moisture and elevated temperatures, which may render it ineffective or even
`
`harmful.
`
`[0010]
`
`In addition to the concerns associated with degradation of an active during
`
`extended exposure to moisture, the conventional drying methods themselves are unable to
`
`provide uniform films. The length of heat exposure during conventional processing, often
`
`referred to as the "heat history", and the manner in which such heat is applied, have a direct
`
`effect on the formation and morphology of the resultant film product. Uniformity is particularly
`
`difficult to achieve via conventional drying methods where a relatively thicker film, which is
`
`well-suited for the incorporation of a drug active, is desired. Thicker uniform films are more
`
`difficult to achieve because the surfaces of the film and the inner portions of the film do not
`
`experience the same external conditions simultaneously during drying. Thus, observation of
`
`relatively thick films made from such conventional processing shows a non-uniform structure
`caused by convection and intermolecular forces and requires greater than 1 0% moisture to
`
`remain flexible. The amount of free moisture can often interfere over time with the drug leading
`
`to potency issues and therefore inconsistency in the final product.
`
`[0011]
`
`Conventional drying methods generally include the use of forced hot air using a
`
`drying oven, drying tunnel, and the like. The difficulty in achieving a uniform film is directly
`
`related to the rheological properties and the process of water evaporation in the film-forming
`
`composition. When the surface of an aqueous polymer solution is contacted with a high
`
`temperature air current, such as a film-forming composition passing through a hot air oven, the
`
`surface water is immediately evaporated forming a polymer film or skin on the surface. This
`
`seals the remainder of the aqueous film-forming composition beneath the surface, forming a
`
`barrier through which the remaining water must force itself as it is evaporated in order to achieve
`
`a dried film. As the temperature outside the film continues to increase, water vapor pressure
`
`builds up under the surface of the film, stretching the surface of the film, and ultimately ripping
`
`4
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`the film surface open allowing the water vapor to escape. As soon as the water vapor has
`
`escaped, the polymer film surface reforms, and this process is repeated, until the film is
`
`completely dried. The result of the repeated destruction and reformation of the film surface is
`
`observed as a "ripple effect" which produces an uneven, and therefore non-uniform film.
`
`Frequently, depending on the polymer, a surface will seal so tightly that the remaining water is
`
`difficult to remove, leading to very long drying times, higher temperatures, and higher energy
`
`costs.
`
`[0012]
`
`Other factors, such as mixing techniques, also play a role in the manufacture of a
`
`pharmaceutical film suitable for commercialization and regulatory approval. Air can be trapped
`
`in the composition during the mixing process or later during the film making process, which can
`
`leave voids in the film product as the moisture evaporates during the drying stage. The film
`
`frequently collapse around the voids resulting in an uneven film surface and therefore, non(cid:173)
`
`uniformity of the fmal film product. Uniformity is still affected even if the voids in the film
`
`caused by air bubbles do not collapse. This situation also provides a non-uniform film in that the
`
`spaces, which are not uniformly distributed, are occupying area that would otherwise be
`
`occupied by the film composition. None of the above-mentioned patents either addresses or
`
`proposes a solution to the problems caused by air that has been introduced to the film.
`
`[0013]
`
`Therefore, there is a need for methods and compositions for film products, which
`
`use a minimal number of materials or components, and which provide a substantially non-self(cid:173)
`
`aggregating uniform heterogeneity throughout the area of the films. Desirably, such films are
`
`. produced through a selection of a polymer or combination of polymers that will provide a
`
`desired viscosity, a film-forming process such as reverse roll coating, and a controlled, and
`
`desirably rapid, drying process which serves to maintain the uniform distribution of non-self(cid:173)
`
`aggregated components without the necessary addition of gel formers or polyhydric alcohols and
`
`the like which appear to be required in the products and for the processes of prior patents, such
`
`as the aforementioned Horstmann and Zerbe patents. Desirably, the films will also incorporate
`
`compositions and methods of manufacture that substantially reduce or eliminate air in the film,
`
`thereby promoting uniformity in the final film product.
`
`5
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`SUMMARY OF THE INVENTION
`
`[0014]
`
`The present invention is directed to rapid-dissolve film products containing at
`
`least one water-soluble polymer including polyethylene oxide alone or in combination with a
`
`hydrophilic cellulosic polymer, wherein the film product is free of added plasticizers.
`
`[0015]
`
`Another embodiment of the rapid-dissolve film product includes at least one
`
`water-soluble polymer containing about 20% to 100% by weight polyethylene oxide, about 0%
`
`to 80% by weight hydroxypropylmethyl cellulose, and about 0% to 80% by weight
`
`hydroxypropyl cellulose; an active component; sucralose; precipitated calcium carbonate;
`
`at least one flavoring; simethicone; water; and at least one colorant, wherein the
`
`film product is free of add~d plasticizers, surfactants, and polyalcohols.
`
`[0016]
`
`Yet another embodiment of the present invention is directed to an edible water-
`
`soluble delivery system in the form of a film composition, which contains at least one water(cid:173)
`
`soluble polymer comprising polyethylene oxide alone or in combination with a polymer selected
`
`from the group consisting of hydroxypropylmethyl cellulose and hydroxypropyl cellulose,
`
`wherein the edible water-soluble delivery system is essentially free of organic solvents,
`
`plasticizers, surfactants, and polyalcohols.
`
`[0017)
`
`The present invention is also directed to processes for making a film having a
`
`substantially uniform distribution of components, including the steps of: (a) combining at least
`
`one water-soluble polymer comprising polyethylene oxide alone or in combination with a
`
`hydrophilic cellulosic polymer, a solvent, and an active component to form a matrix with a
`
`uniform distribution of the components; (b) forming a film from the matrix; and (c) drying the
`
`film, wherein the film is free of added plasticizers.
`
`BRIEF DESCRIPTION OF THE DRAWINGS
`Figure 1 shows a side view of a package containing a unit dosage film of the
`
`[0018)
`
`present invention.
`
`6
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`,,
`
`[0019]
`
`Figure 2 shows a top view of two adjacently coupled packages containing
`
`individual unit dosage fonns of the present invention, separated by a tearable perforation.
`
`[0020]
`
`Figure 3 shows a side view of the adjacently coupled packages of Figure 2
`
`arranged in a stacked configuration.
`
`[0021]
`. dosage fonns, dispenser containing the packaged unit dosage fonns in a stacked configuration.
`
`Figure 4 shows a perspective view of a dispenser for dispensing the packaged unit
`
`[0022]
`
`Figure 5 is a schematic view of a roll of coupled unit dose packages of the present
`
`invention.
`
`[0023]
`
`Figure 6 is a schematic view of an apparatus suitable for preparation of a pre-mix,
`
`addition of an active, and subsequent fonnation of the film.
`
`[0024]
`
`Figure 7 is a schematic view of an apparatus suitable for drying the films of the
`
`present invention.
`
`[0025]
`
`invention.
`
`Figure 8 is a sequential representation of the drying process of the present
`
`[0026]
`
`Figure 9 is a photographic representation of a film dried by conventional drying
`
`processes.
`
`[0027]
`
`Figure 10 is a photographic representation of a film dried by conventional drying
`
`processes.
`
`[0028]
`
`Figure 11 is a photographic representation of a film dried by conventional drying
`
`processes.
`
`[0029]
`
`Figure 12 is a photographic representation of a film dried by conventional drying
`
`processes.
`
`7
`
`RBP_TEVA05018720
`
`DRL - EXHIBIT 1017
`DRL013
`
`

`
`[0030]
`
`Figure 13 is a photographic representation of a film dried by conventional drying
`
`processes.
`
`[0031]
`
`processes.
`
`[0032]
`
`processes.
`
`Figure 14 is a photographic representation of a film dried by conventional drying
`
`Figure 15 is a photographic representation of a film dried by conventional drying
`
`[0033]
`
`Figure 16 is a photographic representation of a film dried by conventional drying
`
`processes.
`
`[0034]
`
`process.
`
`Figure 17 is a photographic representation of a film dried by the inventive drying
`
`[0035)
`
`Figure 18 is a photomicrographic representation of a film containing fat coated
`particles dried by the inventive drying process.
`
`[0036]
`
`Figure 19 is a photomicrographic representation of a film containing fat coated
`particles dried by the inventive drying process.
`
`[0037]
`
`Figure 20 is a photomicrographic representation of a film containing fat coated
`particles dried by the inventive drying process.
`
`[0038]
`
`Figure 21 is a photomicrographic representation of a film containing fat coated
`
`particles dried by the inventive drying process.
`
`[0039]
`
`Figure 22 is a photomicrographic representation of a film containing fat coated
`
`particles dried by the inventive drying process.
`
`8
`
`RBP_TEVA05018721
`
`DRL - EXHIBIT 1017
`DRL014
`
`

`
`It
`
`[0040]
`
`Figure 23 is a photomicrographic representation of a film containing fat coated
`
`particles dried by the inventive drying process.
`
`[0041]
`
`Figure 24 is a photomicrographic representation of a film containing fat coated
`
`particles dried by the inventive drying process.
`
`[0042]
`
`Figure 25 is a photomicrographic representation of a film containing fat coated
`
`particles dried by the inventive drying process.
`
`[0043]
`
`Figure 26 is a photomicrographic representation of fat coated particles not in film,
`
`heated for 9 minutes at 80°C.
`
`[0044]
`
`Figure 27 is a photomicrographic representation of fat coated particles not in film,
`
`heated for 9 minutes at 80°C.
`
`[0045]
`
`Figure 28 is a photomicrographic representation of fat coated particles at room
`
`temperature prior to processing.
`
`[0046]
`
`Figure 29 is a photomicrographic representation of fat coated particles at room
`
`temperature prior to processing.
`
`[0047]
`
`Figure 30 is a photomicrographic representation of fat coated particles at room
`
`temperature prior to processing.
`
`[0048]
`
`Figure 31 is a photomicrographic representation of fat coated particles at room
`
`temperature prior to processing.
`
`[0049]
`
`Figure 32 is a graphical representation of a microarray on the blood of a human
`
`after ingestion by the human of a film of the present invention containing a bovine derived
`
`protein.
`
`9
`
`RBP_TEVA05018722
`
`DRL - EXHIBIT 1017
`DRL015
`
`

`
`••
`
`I
`
`[0050]
`
`Figure 33 is a graphical representation of the temperature differential between the
`
`inside and outside of a film of the present invention during drying.
`
`[0051]
`
`Figure 34 is a graphical representation of the temperature differential between the
`
`inside and outside of a film of the present invention during drying.
`
`[0052]
`
`Figure 35 is a schematic representation of a continuously-linked zone drying
`
`apparatus in accordance with the present invention.
`
`[0053]
`
`Figure 36 is a schematic representation of a separate zone drying apparatus in
`
`accordance with the present invention.
`
`[0054)
`
`Figure 37 is a schematic representation of a extrusion device for use in producing
`
`films of the present invention.
`
`DETAILED DESCRIPTION OF THE INVENTION
`
`[0055)
`
`For the purposes of the present invention the term non-self-aggregating uniform
`
`heterogeneity refers to the ability of the films of the present invention, which are formed from
`
`one or more components in addition to a polar solvent, to provide a substantially reduced
`
`occurrence of, i.e. little or no, aggregation or conglomeration of components within the film as is
`
`normally experienced when films are formed by conventional drying methods such as a high(cid:173)
`
`temperature air-bath using a drying oven, drying tunnel, vacuum drier, or other such drying
`
`equipment. The term heterogeneity, as used in the present invention, includes films that will
`
`incorporate a single component, such as a polymer, as well as combinations of components, such
`
`as a polymer and an active. Uniform heterogeneity includes the substantial absence of
`
`aggregates or conglomerates as is common in conventional mixing and heat drying methods used
`
`to form films.
`
`[0056)
`
`Furthermore, the films of the present invention have a substantially uniform
`
`thickness, which is also not provided by the use of conventional drying methods used for drying
`
`10
`
`RBP_TEVA05018723
`
`DRL - EXHIBIT 1017
`DRL016
`
`

`
`.,1
`
`water-based polymer systems. The absence of a uniform thickness detrimentally affects
`
`uniformity of component distribution throughout the area of a given film.
`
`[0057)
`
`The film products of the present invention are produced by a combination of a
`
`properly selected polymer and a polar solvent, optionally including an active ingredient as well
`
`as other fillers known in the art. These films provide a non-self-aggregating uniform
`
`heterogeneity of the components within them by utilizing a selected casting or deposition method
`
`and a controlled drying process. Examples of controlled drying processes include, but are not
`
`limited to, the use ofthe apparatus disclosed in U.S. Patent No. 4,631,837 to Magoon
`("Magoon"), herein incorporated by reference, as well as hot air impingement across the bottom
`
`substrate and bottom heating plates. Another drying technique for obtaining the films of the
`
`present invention is controlled radiation drying, in the absence of uncontrolled air currents, such
`
`as infrared and radio frequency radiation (i.e. microwaves).
`
`[0058)
`
`The objective of the drying process is to provide a method of drying the films that
`
`avoids complications, such as the noted "rippling" effect, that are associated with conventional
`
`drying methods and which initially dry the upper surface of the film, trapping moisture inside. In
`
`conventional oven drying methods, as the moisture trapped inside subsequently evaporates, the
`
`top surface is altered by being ripped open and then reformed. These complications are avoided
`
`by the present invention, and a uniform film is provided by drying the bottom surface of the film
`
`first or otherwise preventing the formation of polymer film formation (skin) on the top surface of
`
`the film prior to drying the depth of the film. This may be achieved by applying heat to the
`
`bottom surface of the film with substantially no top air flow, or alternatively by the introduction
`
`of controlled microwaves to evaporate the water or other polar solvent within the film, again
`
`with substantially no top air flow. Yet alternatively, drying may be achieved by using balanced
`
`fluid flow, such as balanced air flow, where the bottom and top air flows are controlled to
`
`provide a uniform film. In such a case, the air flow directed at the top of the film should not
`
`create a condition which would cause movement of particles present in the wet film, due to
`
`forces generated by the air currents. Additionally, air currents directed at the bottom of the film
`
`should desirably be controlled such that the film does not lift up due to forces from the air.
`
`Uncontrolled air currents, either above or below the film, can create non-uniformity in the final
`
`11
`
`RBP_TEVA05018724
`
`DRL - EXHIBIT 1017
`DRL017
`
`

`
`film products. The humidity level of the area surrounding the top surface may also be
`
`appropriately adjusted to prevent premature closure or skinning of the polymer surface.
`
`[0059]
`
`This manner of drying the films provides several advantages. Among these are
`
`the faster drying times and a more uniform surface of the film, as well as uniform distribution of
`
`components for any given area in the film. In addition, the faster drying time allows viscosity to
`
`quickly build within the film, further encouraging a uniform distribution of components and
`
`decrease in aggregation of components in the final film product. Desirably, the drying of the
`
`film will occur within about ten minutes or fewer, or more desirably within about five minutes or
`
`fewer.
`
`[0060]
`
`The present invention yields exceptionally uniform film products when attention
`
`is paid to reducing the agg