Details for Patent: 5,958,446

Summary for Patent: 5,958,446

Title:	Solubility parameter based drug delivery system and method for altering drug saturation concentration
Abstract:	The method of adjusting the saturation concentration of a drug in a transdermal composition for application to the dermis, which comprises mixing polymers having differing solubility parameters, so as to modulate the delivery of the drug. This results in the ability to achieve a predetermined permeation rate of the drug into and through the dermis. In one embodiment, a dermal composition of the present invention comprises a drug, an acrylate polymer, and a polysiloxane. The dermal compositions can be produced by a variety of methods known in the preparation of drug-containing adhesive preparations, including the mixing of the polymers, drug, and additional ingredients in solution, followed by removal of the processing solvents. The method and composition of this invention permit selectable loading of the drug into the dermal formulation and adjustment of the delivery rate of the drug from the composition through the dermis, while maintaining acceptable shear, tack, and peel adhesive properties.
Inventor(s):	Jesus Miranda, Steven Sablotsky
Assignee:	Noven Pharmaceuticals Inc
Application Number:	US08/433,754
Patent Claim Types: see list of patent claims	Composition; Compound; Process; Device;

# US Patent 5,958,446: Scope, Claim Analysis, Expiration, and Transdermal Drug-Delivery Patent Landscape

US Patent 5,958,446 covers transdermal pressure-sensitive adhesive compositions that combine a polyacrylate with a second polymer, principally a polysiloxane or hydrocarbon polymer, to control drug permeation through the skin. The patent reaches broad composition claims, narrower formulation ranges, drug-specific embodiments, patch structures, and transdermal administration methods.

The patent issued on September 28, 1999. Its enforceable term has expired. The patent therefore presents historical relevance for products such as estradiol and norethindrone acetate patches, but it does not create a current US exclusionary barrier to generic or follow-on transdermal products. Its claim language remains relevant for prior-art analysis, validity reviews, freedom-to-operate studies involving continuation patents, and interpretation of later transdermal adhesive patents. [1]

What technology does US Patent 5,958,446 protect?

The patent protects a drug-containing pressure-sensitive adhesive in which two polymer systems are blended to adjust drug solubility, adhesive performance, and skin permeation.

The core architecture has four elements:

1. A polyacrylate.
2. A second polymer, principally a polysiloxane or hydrocarbon polymer.
3. A therapeutically effective drug.
4. A pressure-sensitive adhesive that modulates drug permeation through the dermis.

The claims expressly exclude polyethylene/vinyl acetate, commonly known as EVA. That exclusion narrows the claim scope against a major transdermal polymer platform but does not exclude all polyethylene-containing materials. Polyethylene, polyisobutylene, polybutadiene, polystyrene, and polyethylene/butylene remain within the hydrocarbon-polymer alternatives recited in claims 47 to 49 and 60.

The invention is directed to the polymer blend as a drug-delivery matrix. It is not limited to a particular patch brand, therapeutic category, drug, backing layer, or release liner unless those features are recited in a dependent claim.

Which claims are independent and commercially important?

The principal independent claims are claims 1, 43, 45, 50, and 51. Claims 70 to 75 add patch construction or specific drug and enhancer combinations through dependent claiming.

Claim	Claim type	Principal limitations	Commercial relevance
1	Composition	Polyacrylate plus polysiloxane or hydrocarbon polymer; drug; pressure-sensitive adhesive; permeation modulation; no EVA	Broadest practical composition claim
43	Composition	Polyacrylate and polysiloxane in specified weight ranges; drug, cosolvent, enhancer	Stronger formulation-specific claim
45	Method	Applying and maintaining a drug-containing adhesive on mammalian skin; blend governed by solubility parameters	Method-of-use and formulation-function claim
50	Composition	Polyacrylate and polysiloxane or hydrocarbon polymer with solubility-parameter difference of at least 4	Quantitative polymer-selection limitation
51	Composition	Polyacrylate plus specified non-polysiloxane polymers	Alternative polymer-platform claim
70-73	Patch structure	Backing layer and releasable release layer	Finished patch configuration
74-75	Drug-specific	Parkinson's disease drug, propylene glycol, fatty-acid enhancer, and levodopa option	Narrow formulation embodiment

Claim 1 is the principal platform claim. It requires the accused product to contain both a polyacrylate and a qualifying second polymer. A product using only a silicone adhesive, only an acrylic adhesive, or EVA as the relevant polymer system would not literally satisfy claim 1.

Claim 43 is narrower because it requires a two-polymer polyacrylate-polysiloxane system and imposes weight ranges. Claim 50 adds a numerical solubility-parameter difference. Claim 45 is broader in the list of possible second polymers but requires a process involving the net solubility parameter of the blend.

How broad is claim 1?

Claim 1 has substantial chemical and therapeutic breadth but meaningful structural limitations.

Polymer limitations

The first polymer must be a polyacrylate. The second must be either:

• A polysiloxane; or
• A hydrocarbon polymer.

The dependent claims identify polyethylene, polystyrene, polyisobutylene, polybutadiene, and polyethylene/butylene as hydrocarbon polymers. Claims 38 and 39 restrict the polymer blend to the claimed polyacrylate and second polymer, subject to the “consisting essentially of” transition.

The patent therefore reaches a wide range of acrylic-silicone and acrylic-hydrocarbon adhesive matrices. It does not cover every two-polymer transdermal adhesive. The second polymer must fall within the claimed categories, and the product must operate as a pressure-sensitive adhesive for dermal administration.

Drug limitations

Claim 1 does not limit the drug to a particular pharmacological class. The dependent claims expressly identify:

• Estrogens and progestational agents.
• Cardioactive drugs.
• Albuterol.
• Pilocarpine.
• Tranquilizers.
• Antipsychotics.
• Local anesthetics.
• Analgesics.
• Nicotine.
• Androgenic steroids.
• Parkinsonian agents.
• Anti-inflammatory agents.
• Anorectics.
• Drug combinations.

The named drugs include estradiol, norethindrone acetate, nitroglycerin, albuterol, alprazolam, haloperidol, lidocaine, fentanyl, nicotine, selegiline, levodopa, ibuprofen, naproxen, and phentermine.

The drug lists do not independently expand claim 1. They narrow the broad composition claim into specific drug embodiments. A product containing an unlisted drug could still fall within claim 1 if all claim 1 limitations were met.

Permeation limitation

Claim 1 requires that the polymer blend “modulates” drug permeation through the dermis. Claims 35 and 36 refine this concept by requiring increased or decreased permeation compared with a composition containing only one of the polymers.

This limitation creates a potential evidentiary issue. A composition may satisfy the structural polymer limitations but still require proof that the blend modulates permeation. The patent’s specification and experimental data would be important in determining whether “modulates” is a meaningful limitation or an inherent result of the claimed polymer combination.

What formulations are protected by the patent?

The most commercially relevant formulations are acrylic-silicone adhesive systems containing estradiol, norethindrone acetate, or both.

Estradiol formulations

Claim 11 covers 17β-estradiol at approximately 1% to 5% by weight. Claims 52 and 53 add dipropylene glycol and estradiol, with claim 53 specifying 17β-estradiol.

These claims target an adhesive matrix in which estradiol is dissolved or dispersed in a polyacrylate-polysiloxane system. Dipropylene glycol functions as a cosolvent and may affect drug partitioning, adhesive properties, and release.

Estradiol and progestin combinations

Claims 54 to 56 cover combinations of an estrogen and a progestational agent, with emphasis on:

• 17β-estradiol;
• Norethindrone; or
• Norethindrone acetate;

in a composition that may include dipropylene glycol and oleic acid.

This claim group is directed to combination hormone-replacement patches and is more commercially specific than claim 1.

Albuterol formulations

Claims 13 and 41 address albuterol. Claim 41 recites:

• Albuterol: approximately 0.3% to 50%;
• Polysiloxane: approximately 14% to 97%;
• Polyacrylate: approximately 2% to 85%;
• Enhancers: up to approximately 20%;
• Cosolvents: up to approximately 30%.

The total ranges overlap broadly and should be analyzed as a formulation-space claim, not as a single fixed recipe.

Other drug classes

Claims 14 to 34 and 61 to 69 extend the claimed platform to cardiovascular drugs, CNS drugs, anesthetics, analgesics, steroids, anti-inflammatory agents, anorectics, and drug combinations. These claims increase the patent’s theoretical field of use but do not necessarily establish commercial relevance for every listed molecule.

How does claim 50 differ from claim 1?

Claim 50 adds a quantitative solubility-parameter requirement. The polyacrylate and second polymer must have solubility parameters that differ by at least 4 (J/cm³)½.

This limitation has two effects:

• It narrows the claim to polymer pairs with a specified degree of solubility-parameter separation.
• It creates a technical dispute over measurement methodology, polymer composition, temperature, molecular-weight distribution, and whether the relevant value is a pure-polymer parameter or a blend parameter.

Claim 50 may be easier to design around than claim 1 if a competing product uses polymer pairs with a smaller solubility-parameter difference. It may also be vulnerable to an indefiniteness or enablement challenge if the patent does not provide a reproducible method for determining the relevant parameter across the full claimed polymer range.

What does claim 45 protect as a method-of-use claim?

Claim 45 covers a process for transdermally administering a drug by applying the adhesive composition to mammalian skin and maintaining skin contact until an effective amount is delivered.

Its polymer list is broader than claim 1. It includes:

• Polysiloxane;
• Polyvinyl chloride;
• Polyvinylidene chloride;
• Polychloroprene;
• Polyacrylonitrile;
• Nylon-6,6;
• Epoxy resin;
• Polybutadiene/acrylonitrile copolymer; and
• Hydrocarbon polymers.

The claim also requires that the polymers have corresponding solubility parameters and that the net solubility parameter of the blend determines drug solubility.

For enforcement, the patentee would need to establish use of the claimed composition and the required polymer and solubility-parameter relationships. A manufacturer may reduce risk by using a different adhesive architecture, a single-polymer matrix, a non-pressure-sensitive reservoir, or a product in which the claimed polymer blend is absent.

What patent-expiration date applies to US 5,958,446?

US Patent 5,958,446 issued on September 28, 1999. Its term expired in the 2016-2017 period based on the patent’s underlying filing and priority records. The patent is expired and cannot support a current US infringement action for activities occurring after expiration. [1]

Milestone	Date or status
Patent issued	September 28, 1999
Patent type	Utility patent
Subject matter	Transdermal drug-delivery adhesive compositions and methods
Current status	Expired
Practical effect	No current US exclusionary right from this patent

Patent-term analysis should distinguish the issued patent from any continuation, divisional, reissue, or related patent. An expired parent patent does not establish that every related family member has expired, although later-filed continuations are also subject to the 20-year term measured from the earliest effective nonprovisional filing under the Uruguay Round Agreements Act framework. [2]

What is the Orange Book status of US 5,958,446?

The patent’s commercial history is associated with transdermal hormone products, particularly estradiol and estradiol/progestin systems. A patent can be relevant to an approved drug product without remaining an active Orange Book barrier.

For an NDA-listed product, an Orange Book patent must claim the drug substance, drug product, or approved method of use and must satisfy FDA listing requirements. A formulation patent covering a particular adhesive matrix may be listed if it claims the approved product or method. [3]

Because US 5,958,446 is expired, it does not create a current Orange Book delay against an ANDA applicant. Any historical listing would have lost practical blocking effect when the patent expired. Current Orange Book analysis must be performed against the specific NDA and product presentation, including any later-listed formulation or method patents. [3]

When did generic applicants face Paragraph IV risk?

A Paragraph IV certification applies when an ANDA applicant asserts that a listed patent is invalid, unenforceable, or will not be infringed. It is relevant only while the patent is listed and unexpired.

For products containing estradiol and norethindrone acetate, a generic applicant historically could have faced Paragraph IV exposure if this patent was listed for the reference product and the proposed patch used the claimed acrylic-silicone or acrylic-hydrocarbon adhesive system.

The main Paragraph IV arguments would have included:

• The proposed patch does not contain both claimed polymers.
• The second polymer is outside the claimed polysiloxane or hydrocarbon categories.
• The product uses EVA, which is expressly excluded from the claims.
• The product does not operate as a pressure-sensitive adhesive.
• The product does not satisfy the claimed weight ranges.
• The product does not meet the solubility-parameter limitation in claim 50.
• The claimed permeation-modulation limitation is not met.
• The claims are invalid for anticipation or obviousness.
• The claims are indefinite because terms such as “modulates,” “therapeutically effective,” or “net solubility parameter” lack objective boundaries.

No current Paragraph IV challenge can revive an expired patent. Litigation involving a separate, unexpired continuation or a different Orange Book patent would require separate claim-chart analysis.

Which companies are relevant to the patent landscape?

Noven Pharmaceuticals

Noven is the most commercially relevant company associated with the acrylic-silicone transdermal platform reflected in the claims. Noven developed and commercialized multiple transdermal products, including estrogen-based patches and combination hormone products. Noven was acquired by Hisamitsu Pharmaceutical in 2016. [4]

Generic transdermal manufacturers

Generic competition has included companies such as Mylan, Teva, Sandoz, Actavis, and other ANDA sponsors, depending on the specific reference product and dosage form. Generic risk is product-specific because an ANDA applicant can avoid a formulation patent by changing the adhesive matrix while preserving the active ingredient, dosage strength, delivery rate, and patch dimensions.

Competing branded platforms

Relevant competitors include products using:

• Acrylic adhesive matrices;
• Silicone adhesive matrices;
• Polyisobutylene-based adhesives;
• Reservoir systems;
• Multilayer matrix systems; and
• EVA or other polymeric drug reservoirs.

A product using a different adhesive family may avoid literal infringement even if it delivers the same drug through the same route.

How strong is the patent estate?

The patent had meaningful breadth when unexpired, but its current legal strength is zero as an enforceable US patent because the term has ended.

Historically, the estate had several strengths:

• Broad drug coverage.
• Broad therapeutic-class coverage.
• Multiple polymer alternatives.
• Composition and process claims.
• Specific estradiol and norethindrone acetate embodiments.
• Patch construction claims.
• Numerical polymer and drug-loading ranges.
• Coverage of increased and decreased permeation.

Its principal weaknesses were claim breadth and functional language. Potential attack points included:

Issue	Relevance
Obviousness	Blending acrylic and silicone pressure-sensitive adhesives may have been challenged as an optimization of known adhesive systems
Enablement	The patent covers many drugs and polymers with materially different physicochemical properties
Written description	Broad Markush lists may not support every polymer-drug combination equally
Indefiniteness	“Modulates,” “net solubility parameter,” and “therapeutically effective amount” require technical interpretation
Inherency	Permeation modulation may be argued to be an unavoidable property of a claimed blend
Claim construction	“Consisting essentially of” and the EVA exclusion affect the scope of unlisted components

What manufacturing and IP barriers remain after expiration?

The patent’s expiration removes the principal patent barrier, but transdermal product development still faces technical and regulatory barriers.

Manufacturers must establish:

• Uniform drug content across the patch.
• Adhesion throughout the labeled wear period.
• Controlled release and skin permeation.
• Stability of the drug and adhesive matrix.
• Acceptable irritation and sensitization profiles.
• Extractables and leachables control.
• Scalable coating, drying, lamination, and die-cutting processes.
• Bioequivalence or equivalent performance under the applicable FDA pathway.

For an ANDA, the applicant must address the reference product’s dosage form, strength, route, performance, and labeling. A different adhesive composition may trigger comparative adhesion, pharmacokinetic, in vitro release, or other product-specific requirements. FDA guidance treats transdermal delivery systems as complex products because adhesive, liner, backing, drug distribution, and release behavior interact. [5]

How does this patent compare with current generic-launch risk?

Risk category	Assessment
Direct infringement of US 5,958,446	None from post-expiration activity
Historical Paragraph IV risk	Material for products using the claimed adhesive platform
Current formulation-patent risk	Depends on later patents and current Orange Book listings
Biosimilar risk	Not applicable; the claimed products are small-molecule transdermal drugs
Generic launch risk	Driven by active patents, regulatory exclusivity, manufacturing complexity, and product-specific bioequivalence
Design-around potential	High through alternate adhesive systems or nonclaimed polymer combinations
Manufacturing barrier	Moderate to high because of coating, adhesion, dose uniformity, and permeation-control requirements
Commercial exposure	Highest for estrogen and estrogen/progestin patches; lower for uncommercialized drug embodiments

Key Takeaways

• US 5,958,446 covers drug-containing pressure-sensitive adhesives based on a polyacrylate blended with a polysiloxane or hydrocarbon polymer.
• The patent expressly excludes polyethylene/vinyl acetate copolymer.
• Claims 1, 43, 45, 50, and 51 are the principal independent claims.
• Claims 11 and 52 to 56 are commercially important for estradiol and estradiol/norethindrone acetate formulations.
• Claim 45 extends the method coverage to additional polymer classes and solubility-parameter concepts.
• The patent issued on September 28, 1999 and expired in the 2016-2017 period.
• It presents no current US infringement barrier or Paragraph IV delay.
• Current launch risk must be assessed against later patents, Orange Book records, formulation patents, method-of-use patents, and regulatory exclusivity for the specific reference product.
• The patent’s historical strengths were breadth and product-specific dependent claims; its principal technical vulnerabilities were functional language, broad polymer and drug lists, and solubility-parameter limitations.
• Biosimilar analysis is not relevant because the patent concerns small-molecule transdermal products.

FAQs About US Patent 5,958,446

Does US 5,958,446 cover all estradiol patches?

No. It covers estradiol patches only when the product also satisfies the claimed polymer-blend, pressure-sensitive adhesive, drug, and permeation-modulation limitations. The patent is expired.

Does using a silicone adhesive alone infringe the patent?

A silicone-only adhesive would not literally meet claim 1, which requires a polyacrylate and a second polymer. Claims must be reviewed individually, including any continuation patents.

Is an EVA transdermal patch covered by US 5,958,446?

The claims expressly exclude polyethylene/vinyl acetate copolymer. An EVA-based product would require separate analysis under any other claim limitations and other patents.

Can a generic manufacturer use the patented acrylic-silicone formulation now?

The expired patent no longer blocks use of the claimed formulation in the United States. The manufacturer must still assess active related patents, FDA requirements, trade secrets, and manufacturing controls.

Is US 5,958,446 relevant to biosimilar litigation?

No. The patent addresses small-molecule transdermal drug-delivery compositions. Biosimilar litigation concerns biologic products and does not apply to the claimed drug platform.

References

1. United States Patent and Trademark Office. (1999). U.S. Patent No. 5,958,446, Transdermal drug delivery compositions and methods.
2. United States Code, 35 U.S.C. § 154. Patent term and adjustment provisions.
3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations.
4. Hisamitsu Pharmaceutical Co., Inc. (2016). Acquisition of Noven Pharmaceuticals, Inc.
5. U.S. Food and Drug Administration. (2020). Transdermal and topical delivery systems: Product development and quality considerations.

Drugs Protected by US Patent 5,958,446

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate

International Family Members for US Patent 5,958,446

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	002355
Austria	122240
Austria	144704
Austria	148633