Details for Patent: 4,892,739

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Summary for Patent: 4,892,739

Title:	Osmotic continuous dispensing oral delivery system containing a pharmaceutically acceptable active agent having a improved core membrane adhesion properties
Abstract:	An osmotic dispensing delivery system suitable for oral administration, containing a pharmaceutically acceptable active agent for the controlled continuous release of about 50 to about 90 percent by weight of said active agent into the gastrointestinal tract at a rate of about 5 to about 12 percent by weight of said agent per hour consisting essentially of:(a) a shaped solid core containing an osmotically active composition comprising an effective amount of a pharmaceutically acceptable active agent, alone or in combination with a pharmaceutically acceptable binder, an osmotically active driving agent, or tabletting lubricant, or mixtures thereof;(b) said core being substantially evenly coated with a discrete layer of a water-soluble, or water-dispersible, and water permeable substantially non-osmotically active solid polymeric binder, said binder layer being present in an amount between about 0.3 percent and about 10 percent of the weight of the core;(c) a semi-permeable shaped wall member impermeable to said active composition and permeable to gastrointestinal fluid, surrounding and adhesively bonded to the binding layer; and(d) at least one passageway in the wall, for dispensing the active agent, in communication with said core and the external environment.
Inventor(s):	Shailesh B. Shah, Arun D. Koparkar
Assignee:	Novartis Corp
Application Number:	US07/185,564
Patent Claim Types: see list of patent claims	Composition; Compound; Delivery; Dosage form;

US Drug Patent 4,892,739: Claim Scope, Expiration, Orange Book Status, and Metoprolol Patent Landscape

US Patent 4,892,739 covers an osmotic oral delivery system for a moderately water-soluble beta blocker, with specific structural and formulation limitations. The patent is directed most specifically to metoprolol salts delivered through a semipermeable cellulose acetate membrane and a controlled osmotic-release core. The patent issued on January 9, 1990, and its ordinary 17-year term expired on January 9, 2007, absent a term adjustment or extension. It therefore does not create a current US barrier to generic metoprolol products.[1]

The commercially important claim issue is not the broad concept of extended-release metoprolol. It is whether a product has the claimed combination of:

• A semipermeable membrane;
• A discrete polymeric binder layer around the core;
• An osmotically active solid core;
• At least one membrane passageway;
• The claimed binder, lubricant, active-agent, and release-rate ranges; and
• A beta blocker, particularly metoprolol or a salt.

What does US Patent 4,892,739 protect?

The patent protects a dosage form rather than metoprolol as a chemical compound. Its independent claim requires a specific osmotic drug-delivery architecture.

Claim element	Requirement in claim 1	Scope significance
Active agent	Moderately water-soluble pharmaceutically active beta blocker	Limits the claim to beta blockers with the required solubility profile
Release profile	About 60% to 90% of active agent delivered at about 5% to 12% of active-agent weight per hour	Functional and quantitative limitation
Outer wall	Semipermeable membrane substantially impermeable to drug and permeable to gastrointestinal fluid	Requires membrane-driven osmotic operation
Intermediate layer	Discrete, water-soluble or water-dispersible, water-permeable, substantially non-osmotically active polymeric binder layer	Distinguishes the system from a simple coated osmotic tablet
Intermediate-layer amount	0.3% to 10% by weight based on the core	Quantitative limitation
Core	Solid osmotically active composition	Excludes liquid or non-osmotic cores
Tableting binder	About 5% to 20% by weight of the core	Core formulation limitation
Lubricant	Zero to about 10% by weight	Optional limitation in claim 1
Osmotic driving agent	Zero to about 80% by weight	Optional limitation in claim 1
Drug	Remainder of the core composition	Requires the active agent to occupy the balance
Passageway	At least one opening through the wall communicating with the core and external environment	Required route for drug release

The claim is a combination claim. A product must satisfy all material limitations of the claim to fall within its literal scope. Omitting the intermediate polymeric binder layer, using a non-osmotic matrix, or employing a release mechanism that does not use a semipermeable wall and passageway would materially change the infringement analysis.

How do claims 2 through 11 narrow the patent?

Claims 2 through 11 add progressively narrower limitations.

Metoprolol and metoprolol salts

Claim 2 identifies metoprolol or a metoprolol salt as the beta blocker. Claim 3 narrows the subject matter to a metoprolol salt. Claim 4 specifies metoprolol fumarate.

The dependent-claim structure matters. Claim 2 is broader than claim 4 because it does not limit the salt to fumarate. It can encompass metoprolol free base and different pharmaceutically acceptable salts, subject to the remaining requirements of claim 1.

The claims do not expressly identify metoprolol succinate in the quoted text. Claim 2 and claim 3, however, are not limited to fumarate. A metoprolol succinate product could potentially fall within those claims if its dosage form also met the membrane, binder-layer, core-composition, passageway, and release-rate limitations.

Cellulose acetate membrane

Claim 5 requires that the wall membrane consist essentially of cellulose acetate. This is narrower than claim 1, which requires a semipermeable membrane but does not identify a particular polymer.

The phrase "consists essentially of" generally permits components that do not materially alter the basic and novel characteristics of the membrane. The legal analysis would focus on membrane composition, permeability, function, and any additional excipients.

Metoprolol dose

Claim 6 requires 25 mg to 500 mg of metoprolol base as a salt in the core. Claim 7 narrows that range to 30 mg to 400 mg.

The use of "metoprolol base as a salt" indicates that the numerical amount is expressed on a metoprolol-base equivalent rather than necessarily on the total salt mass. For example, the weight of metoprolol succinate in a tablet would not necessarily equal the stated metoprolol-base amount.

Lubricant and binder limitations

Claim 8 limits the tableting lubricant to 1% to 5% by weight. Claim 9 identifies magnesium stearate as the lubricant.

Claim 10 requires hydroxypropyl methylcellulose, polyvinylpyrrolidone, or a mixture of those materials as the tableting binder in the core.

Claim 11 applies those same polymer families to the discrete binder layer and permits polyethylene glycol in an amount of up to 50% of the specified binder-layer composition. The claim language should be construed carefully because the phrase "up to a total of 50% of polyethyleneglycol" can raise questions about whether the percentage is calculated against the binder-layer polymer system or the complete dosage form.

What formulation is required by the patent?

The protected dosage form has three physically distinct regions:

1. An inner solid core containing metoprolol or another beta blocker.
2. A discrete polymeric binder layer surrounding or defining the core.
3. An external semipermeable membrane containing one or more delivery passageways.

The core can contain:

• Approximately 5% to 20% tableting binder;
• Zero to approximately 10% lubricant;
• Zero to approximately 80% osmotic driving agent; and
• The balance as active agent.

The osmotic driving agent is optional under claim 1. That point creates an important claim-construction issue. The claim describes an "osmotically active composition" but permits zero osmotic driving agent. The osmotic function could therefore arise from the active agent, the binder, salts, or other core components rather than from a separately added osmogen.

Typical osmotic systems use materials such as sodium chloride, sugars, or other osmotically active excipients. The claim does not require a named osmogen, which gives it broader composition coverage than a claim limited to a specific salt or sugar.

How does the release-rate limitation affect infringement?

The system must deliver about 60% to 90% of the active agent at a substantially continuous rate of about 5% to 12% by weight of the total active agent per hour.

This is a significant limitation. A product that contains the same membrane and core components but releases the drug through a materially different profile could avoid literal infringement of claim 1. The analysis would require dissolution or in vivo release data, the test conditions used, and a determination of whether the profile is "substantially continuous."

The range also appears to create a timing relationship. At a release rate of 5% to 12% per hour, delivery of 60% to 90% of the dose would generally occur over approximately five to eighteen hours, subject to the meaning of the "about" ranges and the actual release curve.

A product does not necessarily avoid the claim merely because it releases the final portion of the dose differently. The claim requires the stated delivery of 60% to 90% of the active agent at the specified substantially continuous rate, not necessarily complete release at that same rate.

What is the patent expiration date for US 4,892,739?

US Patent 4,892,739 issued on January 9, 1990. For a pre-June 8, 1995 US application, the ordinary term was generally 17 years from issuance, subject to terminal disclaimers, patent term adjustment, patent term extension, and other statutory modifications.[1][2]

Event	Date
Patent issued	January 9, 1990
Ordinary 17-year term from issuance	January 9, 2007
Current enforceability	Expired
Current Paragraph IV risk based on this patent	None
Current Orange Book blocking effect	None from this expired patent

The patent cannot support a current infringement action against a generic manufacturer. Any damages claim would be limited to the enforceable period and would also depend on proof of infringement, validity, standing, and other litigation requirements.

What is the Orange Book status of US 4,892,739?

An issued patent and an Orange Book-listed patent are different categories.

The FDA Orange Book records patents submitted by NDA holders for approved drug products under the applicable FDA listing rules. A patent may be technically relevant to a dosage form without being listed for a particular NDA. Conversely, an Orange Book-listed patent may cover a method of use, formulation, or product presentation rather than the active ingredient itself.[3]

US 4,892,739 should be treated as an expired historical formulation patent. It is not a current Orange Book barrier to an abbreviated new drug application because an expired patent does not block approval or commercial launch.

For a live product such as extended-release metoprolol, the relevant Orange Book review must focus on:

• The specific reference listed drug;
• Current patent listings submitted by the NDA holder;
• Patent expiration dates;
• Any pediatric exclusivity attached to listed patents;
• Any active regulatory exclusivity; and
• Whether the generic applicant filed Paragraph IV certifications against later patents.

The status of 4,892,739 alone does not establish the Orange Book status of a particular metoprolol product.

When did generic metoprolol lose exclusivity?

Metoprolol is a small-molecule beta blocker, not a biologic. Biosimilar rules do not apply. Generic competition proceeds through the ANDA pathway under section 505(j) of the Federal Food, Drug, and Cosmetic Act.[4]

The commercial exclusivity analysis has several separate components:

Exclusivity type	Relevance to metoprolol
Compound patent	Protects the chemical entity, if unexpired
Formulation patent	Protects the delivery system or dosage form
Method-of-use patent	May cover a labeled indication
New chemical entity exclusivity	Historically applicable only during the statutory period
Three-year clinical-investigation exclusivity	May apply to certain approval supplements
Pediatric exclusivity	Adds six months to qualifying exclusivity or patent terms
Orphan exclusivity	Generally not central to ordinary hypertension products
FDA approval of ANDAs	Permits generic competition after blocking patents and exclusivities expire

The original metoprolol compound patent and the patent at issue here are no longer enforceable. Generic entry therefore depends on later patents, regulatory exclusivities, manufacturing capabilities, and the reference product's current FDA status, not on US 4,892,739.

Which companies challenged extended-release metoprolol patents?

The historically important US disputes concerning Toprol-XL and generic extended-release metoprolol involved later product-specific patents and ANDA filings. Publicly reported generic applicants and manufacturers in the broader Toprol-XL litigation and market included firms such as Andrx, Eon Laboratories, Sandoz, and Dr. Reddy's Laboratories.

Those proceedings should not be attributed automatically to US 4,892,739. A litigation search must distinguish:

• The patent asserted;
• The NDA product involved;
• The ANDA filer;
• The court and docket;
• The certification made under Paragraph IV;
• Any preliminary injunction;
• The settlement terms; and
• The date of generic launch.

Because US 4,892,739 expired in 2007, any later Toprol-XL litigation would have depended primarily on later patents, not on the expired patent itself. Settlements involving later patents also would not revive or extend the term of 4,892,739.

What patent landscape surrounds metoprolol extended-release products?

The relevant patent landscape is broader than the 11 claims in US 4,892,739.

Compound and salt patents

Compound patents generally cover metoprolol itself or a specific salt. These patents are distinct from dosage-form claims. A salt patent can create a separate barrier even when an osmotic-delivery patent has expired.

Formulation patents

Formulation patents may cover:

• Osmotic delivery;
• Extended-release matrices;
• Coated multiparticulates;
• Specific membrane polymers;
• Pore-forming agents;
• Controlled release through diffusion;
• Tablet hardness and excipient ratios; and
• Salt-specific release performance.

US 4,892,739 is strongest against products that replicate its layered osmotic architecture. It is less relevant to matrix tablets, multiparticulate capsules, or diffusion-controlled systems that do not have the claimed membrane-and-passageway structure.

Method-of-use patents

Method claims may cover treatment of hypertension, angina, heart failure, migraine, or other cardiovascular conditions using metoprolol. These claims are assessed separately from the dosage-form claims.

A generic applicant may certify that a listed method-of-use patent is not infringed or is invalid while carving the patented indication from its labeling under the section viii statement procedure, where permitted.[4]

Manufacturing patents

Manufacturing-related rights may cover:

• Preparation of metoprolol salts;
• Granulation and compression;
• Membrane coating;
• Laser or mechanical passageway formation;
• Control of coating thickness;
• Osmogen incorporation; and
• In-process dissolution testing.

These patents can create practical barriers even when the finished dosage form is outside the expired claims of US 4,892,739. They can also affect licensing negotiations, contract manufacturing, and technology-transfer costs.

How strong is the patent estate for US 4,892,739?

The patent was technically meaningful when unexpired because it combined a drug class, a dosage-form structure, and a controlled-release profile. Its principal strengths were:

• A broad independent claim directed to beta blockers;
• Specific metoprolol claims;
• Coverage of metoprolol salts;
• A cellulose acetate membrane limitation in a dependent claim;
• Quantitative core and binder-layer ranges; and
• A defined release-rate requirement.

Its principal weaknesses were:

• The requirement for a highly specific physical architecture;
• The need to prove the claimed release profile;
• Potential design-around options using matrix or multiparticulate systems;
• Possible ambiguity in the interpretation of "moderately water-soluble";
• Potential disputes over "substantially continuous" release;
• The optional osmotic-driving-agent limitation; and
• Expiration of the patent term.

As a current commercial asset, the patent has no enforceable exclusivity value. Its remaining value is historical and technical: it can help identify prior-art concepts, claim language, formulation design strategies, and potential validity issues for later patents.

What generic launch scenarios exist today?

A generic manufacturer of extended-release metoprolol may pursue several development routes:

Product design	Relationship to US 4,892,739	Commercial implication
Same osmotic membrane architecture	Higher historical relevance	Must be assessed against later patents, but 4,892,739 itself is expired
Matrix tablet	Usually structurally different	May reduce exposure to the claimed passageway system
Coated multiparticulate system	May avoid the solid-core architecture	Requires separate bioequivalence strategy
Different metoprolol salt	May avoid salt-specific claims	Does not necessarily avoid broader metoprolol claims in expired patents
Different membrane polymer	May avoid cellulose acetate dependent claim	Does not alone avoid claim 1
Modified release profile	May avoid the rate limitation	Must still satisfy FDA bioequivalence requirements
Same active ingredient with different excipient system	Could avoid dependent claims	Claim 1's broader combination still requires review

The principal current risks are therefore later patent rights, FDA bioequivalence requirements, product quality, supply-chain capability, and any active exclusivity associated with the specific reference product.

What is the geographic scope of US 4,892,739?

The patent is a US right. Its enforceable scope was limited to the United States and to acts falling within US patent jurisdiction. It did not create protection in Europe, Canada, Japan, or other markets.

Parallel applications or patents may have existed in other jurisdictions, but they require separate family-level review. Expiration in the United States does not establish expiration elsewhere. Conversely, foreign patent rights do not restore US exclusivity.

Key Takeaways

• US 4,892,739 covers a layered osmotic oral delivery system for beta blockers, with specific metoprolol and metoprolol-salt claims.
• Claim 1 requires a semipermeable membrane, a discrete polymeric binder layer, a solid osmotic core, a passageway, and a defined release profile.
• Claims 2 through 4 focus on metoprolol, metoprolol salts, and metoprolol fumarate.
• Claims 5 through 11 narrow the membrane, dose, lubricant, binder, and polymer-layer composition.
• The patent issued January 9, 1990, and its ordinary term expired January 9, 2007.
• The patent is not a current US exclusivity barrier and cannot support a current Paragraph IV challenge.
• It is not a biosimilar patent issue because metoprolol is a small-molecule drug.
• Current generic risk depends on later formulation, method-of-use, manufacturing, and product-specific patents, together with FDA exclusivity and bioequivalence requirements.
• Historical Toprol-XL litigation should be separated from this patent because later patents, rather than US 4,892,739, drove the relevant commercial disputes.
• The patent remains relevant as prior art and as a technical reference for osmotic metoprolol delivery, but it has no current enforceable commercial value.

FAQs

Does US 4,892,739 cover metoprolol succinate?

Potentially under the broader metoprolol and metoprolol-salt claims, but only if the product also satisfies the claimed osmotic membrane, binder layer, core, passageway, and release-profile limitations. The patent does not expressly name metoprolol succinate in the quoted claims.

Does the patent cover a conventional extended-release matrix tablet?

Generally, no. The claims require a semipermeable wall membrane and at least one passageway communicating with the core. A conventional hydrophilic matrix tablet without that structure would ordinarily be outside the literal claim architecture.

Can an expired patent be asserted in a Paragraph IV certification?

No. Paragraph IV certifications address patents listed for a reference product that are alleged to be invalid, unenforceable, or not infringed. An expired patent does not create a current approval block.

Does expiration of US 4,892,739 eliminate all metoprolol patent risk?

No. Later patents may cover a particular salt, formulation, manufacturing process, method of use, or reference product. Each patent must be reviewed independently.

Is metoprolol eligible for a biosimilar pathway?

No. Metoprolol is a chemically synthesized small-molecule active ingredient. Generic versions are ordinarily reviewed through the ANDA pathway, not the biologics license application and biosimilar pathway.

References

1. United States Patent and Trademark Office. (1990). US Patent No. 4,892,739, Osmotic dispensing system.
2. United States Code, 35 U.S.C. §§ 154, 156, and 271.
3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
4. Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 355(j).

Drugs Protected by US Patent 4,892,739

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 4,892,739

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	75939
Australia	3268789
Australia	618083