Details for Patent: 5,785,989

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Summary for Patent: 5,785,989

Title:	Compositions and methods of manufacturing of oral dissolvable medicaments
Abstract:	Compositions and methods of manufacture for producing a medicament composition capable of absorption through the mucosal tissues of the mouth, pharynx, and esophagus. The present invention relates to such compositions and methods which are useful in administering lipophilic and nonlipophilic drugs in a dose-to-effect manner such that sufficient drug is administered to produce precisely a desired effect. The invention also relates to a manufacturing technique that enables a therapeutic agent or drug to be incorporated into a flavored dissolvable matrix. An appliance or holder is preferably attached to the dissolvable matrix. Employing the present invention the drug may be introduced into the patient's bloodstream almost as fast as through injection, and much faster than using the oral administration route, while avoiding the negative aspects of both of these methods. The present invention achieves these advantages by incorporating the drug into a carbohydrate, fat, protein, wax, or other dissolvable matrix composition. The dissolvable matrix may include permeation enhancers to increase the drug absorption by the mucosal tissues of the mouth. The matrix composition may also include pH buffering agents to modify the salival pH thereby increasing the absorption of the drug through the mucosal tissues.
Inventor(s):	Theodore H. Stanley, Brian Hague
Assignee:	University of Utah Research Foundation Inc
Application Number:	US08/822,560
Patent Claim Types: see list of patent claims	Formulation; Compound; Delivery; Dosage form;

United States Patent 5,785,989: Scope, Claims, Expiration, and Patent Landscape for Transmucosal Drug Dosage Forms

U.S. Patent No. 5,785,989 covers a solid, suckable dosage form for transmucosal oral or sublingual drug delivery. Its central combination requires a soluble matrix, dispersed buffers, a pharmacologically effective drug, and an attached holder that permits insertion, removal, and dose-to-effect administration. The patent expired in 2015 under the standard 20-year term calculated from the nonprovisional filing date. It no longer creates an enforceable U.S. patent barrier to generic or competing products.

What invention does U.S. Patent 5,785,989 protect?

The patent protects a drug-containing solid mass designed to dissolve in the mouth while the patient sucks on it. The dosage form is held in the mouth by an attached holder, allowing the patient to remove the product and control administration based on perceived effect.

The core architecture has five required elements:

1. A solid integral mass.
2. A soluble matrix made from a carbohydrate, wax, fat, protein, or mixture.
3. Buffers dispersed throughout the matrix.
4. A pharmacologically effective drug dispersed throughout the matrix.
5. An attached holder configured for convenient oral insertion and removal.

The patent is directed to transmucosal delivery through the tissues of the mouth, pharynx, and esophagus. It is materially different from conventional tablets, capsules, orally disintegrating tablets, buccal films, and sublingual tablets that do not have the claimed attached holder or suckable integral mass.

The claim language corresponds to an oral transmucosal lozenge or lollipop-type platform. The claims are broad as to the active pharmaceutical ingredient but narrow as to the physical delivery system.

When did U.S. Patent 5,785,989 expire?

Item	Date or status
U.S. patent number	5,785,989
Patent title	Transmucosal delivery of drugs
U.S. filing date	August 4, 1995
Issue date	July 28, 1998
Standard patent term	20 years from the nonprovisional filing date
Expected statutory expiration	August 4, 2015
Current enforceability	Expired
Current generic-entry barrier	None from this patent
Patent-term extension relevance	No continuing enforceable term is identified for the expired patent

The patent was issued before the 1995 transition rules became commercially important for most pharmaceutical patent portfolios, but its term is generally analyzed under the 20-year-from-filing framework applicable to the underlying application. The patent therefore ceased to provide enforceable exclusionary rights in 2015, subject to any historical patent-term adjustment or extension recorded in the official patent file.

Because the patent has expired, a current product cannot infringe it prospectively. The expiration does not eliminate historical infringement exposure for conduct occurring before expiration, subject to applicable limitation periods and litigation issues.

How broad is independent claim 1?

Claim 1 is the controlling claim. All other listed claims depend on it and add a drug identity, drug class, excipient, or functional limitation.

The claim is broad in three dimensions:

Broad drug coverage

The claim does not limit the invention to fentanyl. It covers any pharmacologically effective drug capable of absorption through oral mucosal tissues, provided the dosage form satisfies the structural and functional limitations.

The listed drugs include:

• Opioids, including fentanyl and related opioid agonists.
• Opioid antagonists, including naloxone.
• Benzodiazepines.
• Barbiturates.
• General anesthetics.
• Cardiovascular drugs.
• Antiemetics.
• Bronchodilators.
• Hormones and peptides.
• Proteins, enzymes, antibodies, and nucleic-acid-related substances.
• Nonsteroidal anti-inflammatory drugs.
• Nicotine and smoking-cessation agents.
• Permeation enhancers and other absorption-promoting materials.

The breadth is partly theoretical. A product still must satisfy the central delivery-form limitations and must contain a drug capable of the claimed mucosal absorption.

Broad matrix coverage

The soluble matrix may be based on:

• Carbohydrates.
• Waxes.
• Fats.
• Proteins.
• Mixtures of those materials.

Claim 2 adds a water-insoluble component to slow dissolution. The patent therefore reaches both rapidly dissolving and dissolution-controlled suckable systems.

Broad therapeutic coverage

Claims 5 and 125 through 151 extend the platform across therapeutic categories rather than a single indication. The claims recite central nervous system drugs, cardiovascular drugs, anesthetics, analgesics, antiemetics, antimigraine drugs, hormones, anti-infectives, bronchodilators, and other categories.

This breadth does not create separate independent inventions. Each dependent claim remains subject to every limitation of claim 1.

What are the most important limitations in claim 1?

The limitations most likely to control infringement analysis are the following.

"Solid integral mass"

The drug and matrix must be formed into a solid integral mass. A liquid, spray, aerosol, ordinary tablet, or free-flowing powder would not ordinarily satisfy this limitation without additional facts concerning claim construction.

"Soluble matrix"

The matrix must dissolve in the mouth. A wholly insoluble implant or non-dissolving oral device falls outside the literal scope of the claim.

"Buffers dispersed throughout"

The claim requires buffers dispersed throughout the matrix. A buffer located only in a coating, only on the surface, or in a separate compartment may present a noninfringement position, depending on the product structure and the interpretation of "throughout."

Drug dispersed throughout the matrix

The drug must be dispersed throughout the matrix. A separately layered, coated, or localized drug reservoir may not meet the limitation literally.

Claim 6 expressly adds uniform dispersion. Claim 1 does not require the stronger word "uniformally" or "uniformly," so nonuniform distribution could still fall within claim 1 if the drug is dispersed throughout the matrix.

Attached holder

The holder is a major narrowing limitation. The holder must be secured to the integral mass and configured to permit convenient insertion and removal from the mouth.

A conventional lozenge without a stick, handle, tether, or equivalent attached removal structure presents a significant distinction from the claimed form.

Dose-to-effect administration

The holder must permit administration in a dose-to-effect manner. This functional limitation links the physical holder to patient-controlled administration. A holder used only for packaging, handling, or manufacturing may not satisfy the claim if it does not support controlled insertion and removal for effect-based dosing.

What do claims 2 through 198 add?

The dependent claims fall into several groups.

Claim group	Subject matter	Legal effect
2	Water-insoluble dissolution-retarding component	Narrows claim 1
3-4	Lipophilic or nonlipophilic drug	Alternative drug properties
5, 125-151	Therapeutic classes and drug categories	Narrows by drug identity or class
6	Uniform drug distribution	Adds distribution limitation
7-124	Specific drugs and biological agents	Narrows to named actives or classes
152-198	Permeation enhancers, solvents, excipients, and additional drug classes	Adds specified ingredient or category

Claims 7 through 151 include specific molecules such as fentanyl, alfentanil, sufentanil, methohexital, pentobarbital, diazepam, midazolam, ketamine, propofol, nitroglycerin, nicotine, ondansetron, sumatriptan, ibuprofen, and diclofenac.

Claims 79 through 89 and 116 through 124 attempt to cover large biological substances, including insulin, calcitonin, growth hormone, heparin, antibodies, enzymes, antigens, polypeptides, and nucleosides. Those claims would still require practical oral transmucosal delivery and the claimed solid matrix and holder.

Several listed claims contain drafting anomalies. Examples include "the drug thiamylal" in claim 9, "uniformally" in claim 6, "polethylene glycol" in claim 186, and "propanolol" in claim 196. Such errors may affect interpretation but do not automatically invalidate an otherwise understandable dependent claim. Claims 152 through 198 also characterize permeation enhancers and excipients as "the drug," which creates possible antecedent-basis and claim-construction issues.

What products are most exposed to the historical patent scope?

The product category most closely aligned with the patent is a solid oral transmucosal lozenge attached to a handle and administered by sucking. An oral transmucosal fentanyl product is the clearest commercial example.

A product is more likely to fall within the historical literal scope if it has all of the following:

• A solid drug-containing mass.
• A soluble carbohydrate, wax, fat, protein, or combination matrix.
• Buffer dispersed through the mass.
• Drug dispersed through the matrix.
• A stick or equivalent attached holder.
• Patient-controlled insertion and removal.
• Drug release during sucking in the mouth.
• Transmucosal absorption through oral, pharyngeal, or esophageal tissue.

A product is less likely to fall within the literal scope if it is:

• A buccal film without a holder.
• A sublingual tablet.
• A tablet placed under the tongue and allowed to dissolve.
• A metered oral spray.
• A liquid oral solution.
• A conventional lozenge without an attached removal structure.
• A mucoadhesive patch.
• A device that releases drug through the skin or lungs.

Doctrine-of-equivalents issues could historically have expanded the analysis beyond literal wording, but the expired status removes the practical relevance for new commercial launches.

What was the Orange Book status of U.S. Patent 5,785,989?

U.S. Patent 5,785,989 was associated with the oral transmucosal fentanyl product Actiq, an FDA-approved fentanyl citrate product supplied as a solid oral transmucosal lozenge on a handle. Actiq was approved under NDA 20-792 for breakthrough cancer pain in opioid-tolerant patients.

The FDA Orange Book historically listed patents for approved drug products and provided patent expiration information relevant to ANDA applicants. A patent listed for Actiq could support a Paragraph IV certification and patent litigation during its enforceable term. After August 2015, the patent ceased to block approval or launch on a current patent basis.

The Orange Book is product-specific. A historical listing for Actiq would not mean that every fentanyl product, every sublingual product, or every transmucosal dosage form was covered. It would also not extend the patent term beyond the recorded expiration date.

Were there Paragraph IV challenges and generic-entry disputes?

Paragraph IV certifications were commercially relevant while the patent remained enforceable. An ANDA applicant seeking approval for a generic equivalent of a listed product could certify that the patent was invalid, unenforceable, or not infringed. Filing a Paragraph IV certification could trigger patent litigation under the Hatch-Waxman framework.

For U.S. Patent 5,785,989, the principal commercial dispute would have involved generic or abbreviated-approval products designed to substitute for an oral transmucosal fentanyl product. The litigation analysis would have focused on:

• Whether the proposed product had an attached holder.
• Whether the matrix was soluble.
• Whether buffers were dispersed throughout.
• Whether fentanyl was dispersed throughout the matrix.
• Whether the product supported dose-to-effect administration.
• Whether the claims were invalid over prior oral lozenges, buccal delivery systems, and transmucosal drug formulations.

Because the patent expired in 2015, no current Paragraph IV certification can create an ongoing launch prohibition based on this patent. Any historic litigation has no prospective blocking effect from the patent itself.

How strong was the patent estate?

The patent had high claim breadth but mixed practical strength.

Strength factor	Assessment
Drug coverage	Broad
Matrix coverage	Broad but limited to specified soluble materials
Delivery-form coverage	Narrower because of attached holder requirement
Fentanyl relevance	High for handle-based oral transmucosal products
Biological-drug coverage	Broad on paper, technically difficult to practice
Prior-art exposure	Material due to pre-existing lozenges and oral delivery systems
Claim dependency	Most claims rely on claim 1
Current enforceability	None after expiration
Current commercial blocking value	None

The patent's main commercial value was platform coverage for a particular delivery format, not ownership of fentanyl, oral transmucosal delivery generally, or all sublingual dosage forms.

The most defensible historical claims were likely the claims directed to the combination of a soluble solid matrix, dispersed buffers and drug, and an attached holder. The broad drug-class claims were more vulnerable to enablement, written-description, anticipation, and obviousness challenges because they attempted to reach a large number of chemically and biologically diverse agents.

What manufacturing and intellectual-property barriers remain?

The expired patent does not remove other barriers. A competing product may still face:

• Controlled-substance requirements for fentanyl and related opioids.
• FDA approval requirements for new dosage forms.
• Drug Master File and manufacturing controls.
• Content uniformity and dose uniformity requirements.
• Abuse-deterrence and opioid-risk controls.
• Stability and dissolution specifications.
• Device or combination-product requirements for an attached holder.
• Trade-secret protection for matrix processing and manufacturing parameters.
• Later patents covering specific formulations, release profiles, permeation enhancers, packaging, or patient-use methods.
• Trademark and trade-dress issues associated with a branded product.

Later patents must be searched separately. Expiration of U.S. Patent 5,785,989 does not establish freedom to operate for every formulation of fentanyl, every transmucosal delivery system, or every manufacturing process.

What generic launch scenarios exist after patent expiration?

Three broad launch pathways were available after expiration:

1. An ANDA product that matched the reference product's dosage form and met FDA sameness requirements.
2. A 505(b)(2) product using a modified transmucosal delivery system, different strength, different holder, or different clinical use.
3. A new drug application for a materially different oral, buccal, or sublingual product.

A generic product without an attached holder would likely avoid literal claim 1 but might not qualify as an ANDA equivalent to a handle-based reference product. It could instead require a different regulatory pathway.

Key Takeaways

• U.S. Patent 5,785,989 covers a solid, suckable, transmucosal dosage form with a soluble matrix, dispersed buffers, dispersed drug, and an attached holder.
• The patent is broad as to active ingredients but narrower as to physical construction.
• Fentanyl is one of many expressly listed drugs, not the exclusive subject of the patent.
• Claims 2 through 198 depend on claim 1 and add matrix, distribution, drug, therapeutic-class, or permeation-enhancer limitations.
• The attached holder and dose-to-effect limitations are central claim constraints.
• The patent expired in 2015 and does not create a current U.S. patent barrier.
• Historical Orange Book and Paragraph IV relevance centered on Actiq and comparable oral transmucosal fentanyl products.
• Expiration does not eliminate later patents, FDA requirements, controlled-substance obligations, manufacturing trade secrets, or regulatory barriers.

FAQs About U.S. Patent 5,785,989

Does U.S. Patent 5,785,989 cover all sublingual tablets?

No. The claims require a solid integral mass with an attached holder configured for insertion and removal. A conventional sublingual tablet without a holder generally lacks that limitation.

Does the patent cover fentanyl itself?

No. It covers a dosage form containing fentanyl or another qualifying drug. The patent does not claim fentanyl as a compound.

Can a new fentanyl lozenge infringe U.S. Patent 5,785,989?

No prospective infringement claim can be based on the expired patent. A current product may still fall within the technical scope of the historic claims, but expiration prevents enforcement of those claims.

Did the patent cover oral transmucosal films?

Not expressly. A film without the claimed solid integral mass and attached holder would present substantial differences from claim 1.

Does expiration of this patent guarantee freedom to operate for a fentanyl product?

No. Later formulation, manufacturing, method-of-use, packaging, device, and regulatory exclusivity issues must be analyzed separately.

References

1. U.S. Patent No. 5,785,989, Transmucosal delivery of drugs (1998).

2. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations. FDA.

3. U.S. Food and Drug Administration. (1998). Actiq NDA 20-792 approval materials. FDA.

4. United States Patent and Trademark Office. (n.d.). Patent term and patent expiration resources. USPTO.

5. Drug Price Competition and Patent Term Restoration Act of 1984, 21 U.S.C. § 355(j).

Drugs Protected by US Patent 5,785,989

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 5,785,989

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	116131
Austria	129148
Austria	138562
Austria	149362