US Patent 4,880,631: Claim Scope, Expiration, Orange Book Status, and Diltiazem Osmotic-Pump Patent Landscape

US Patent 4,880,631 protects a specific controlled-release osmotic delivery system for diltiazem L-malate. Its central limitations are a diltiazem L-malate core, sodium bitartrate in an 80% to 150% weight ratio relative to the drug, and a porous, water-insoluble semipermeable wall with specified permeability, reflection coefficient, and pore-former ranges. The patent issued in 1989 and, absent an unusual term adjustment or restoration, its enforceable US term expired in 2006. The claims therefore present historical technology coverage rather than a current US blocking right.

The patent is narrower than a general diltiazem extended-release claim. It does not cover all diltiazem formulations, all osmotic systems, or all controlled-release diltiazem products.

What does US Patent 4,880,631 cover?

The patent covers an osmotic pump that delivers diltiazem L-malate through a porous, water-insoluble wall. Claim 1 is the principal device claim. Claim 20 separately covers an admixture of diltiazem L-malate and sodium bitartrate in a drug-delivery device.

The essential structure of claim 1 is:

Claim element	Required limitation
Drug	Therapeutically effective amount of diltiazem L-malate
Osmotic agent	Sodium bitartrate at 80% to 150% by weight relative to diltiazem L-malate
Wall	Water-insoluble, rate-controlling wall
Wall polymer	Water-permeable but solute-impermeable polymer
Pore former	pH-insensitive additive dispersed throughout the wall
Pore-former level	0.1% to 60% by weight of polymer plus pore former
Fluid permeability	6.96 × 10^-18 to 6.96 × 10^-14 cm³·sec/g
Reflection coefficient	Less than 0.5

A product must satisfy all limitations of an asserted claim for literal infringement. A device using diltiazem hydrochloride rather than diltiazem L-malate would not literally satisfy the drug-salt limitation.

What are the independent claims in US 4,880,631?

Claim 1: osmotic-pump device claim

Claim 1 is an apparatus claim directed to a completed delivery device. It requires the drug-containing core and the rate-controlling wall. The claim is not limited to a particular dosage strength, wall thickness, pore diameter, polymer species, or pore former, except where those characteristics are needed to satisfy the expressly recited functional parameters.

The claim has several cumulative technical requirements:

Diltiazem must be present as the L-malate salt.
Sodium bitartrate must be present at 80% to 150% by weight relative to the diltiazem L-malate.
The wall must be water-insoluble.
The wall must permit water transport while resisting solute transport.
The wall must contain a pH-insensitive pore-forming additive.
The pore former must fall within the stated concentration range.
The wall must fall within the claimed permeability and reflection-coefficient ranges.

The permeability and reflection-coefficient limitations are potentially significant infringement barriers. They require technical testing and claim-construction analysis rather than simple review of an ingredient list.

Claim 20: composition or admixture claim

Claim 20 covers:

An admixture of diltiazem L-malate with between 80 and 150 percent by weight of sodium bitartrate in a drug delivery device for controlled release.

Claim 20 is materially broader than claim 1 because it does not expressly recite the porous wall, wall polymer, pore former, permeability range, or reflection coefficient. It remains limited by:

diltiazem L-malate;
sodium bitartrate at the specified relative amount;
an admixture in a drug-delivery device; and
controlled release to an environment of use.

The claim’s breadth depends heavily on how “drug delivery device” and “controlled release” are construed. It does not expressly require an osmotic pump, although the specification and claim context could influence construction. The claim also contains the apparent typographical spelling “dilitiazem,” but the intended reference is diltiazem L-malate.

How do claims 2 through 19 narrow the patent?

The dependent claims add dosage, wall, polymer, pore-former, additive, and combination-product limitations.

Claim	Added limitation
2	Diltiazem L-malate from 30 mg to 500 mg
3	Sodium bitartrate from 30 mg to 500 mg
4	Solid pore former at 0.1% to 50% and/or liquid pore former at 0.1% to 40%, subject to 60% total
5	Wall thickness of 20 to 500 microns; pores of 10 angstroms to 25 microns
6	Reflection coefficient below 0.1
7	Plasticizer and flux-regulating additives up to 50 parts per 100 parts of wall materials; surfactant up to 40 parts
8	Wall thickness of 1 to 1,000 microns; 5% to 95% of pores from 10 angstroms to 100 microns
9	Broad polymer group, including cellulose esters, acylated polysaccharides, polyurethane, acrylic and methacrylic polymers, poly(ortho ester)s, and polyacetals
10	Cellulose esters and acylated polysaccharides
11	Polyurethanes and acrylic or methacrylic polymers
12	Poly(ortho ester)s and polyacetals
13	Water, alkali-metal salts, alkaline-earth-metal salts, saccharides, aliphatic polyols, aromatic polyols, or mixtures
14	Total pore former at 0.1% to 50%
15	Polyethylene glycol, sorbitol, glucose, or mixtures
16	External layer containing a pharmaceutically acceptable carrier and cardiovascular agent
17	Specified cardiovascular-agent classes
18	Cardiovascular agent is an ACE inhibitor
19	ACE inhibitor is captopril, enalapril, or lisinopril

Claims 16 through 19 describe a combination product with an external cardiovascular-agent layer. They do not cover a conventional fixed-dose tablet merely because it contains diltiazem and another cardiovascular drug. The claim requires the external-layer arrangement recited in claim 16.

What formulations are protected by US 4,880,631?

The strongest formulation coverage is directed to an osmotic core containing:

diltiazem L-malate;
sodium bitartrate at 80% to 150% by weight relative to the diltiazem L-malate; and
a porous, water-insoluble wall.

The patent expressly identifies several wall and pore-former categories.

Wall materials

Claim 9 identifies:

cellulose esters;
acylated polysaccharides;
polyurethanes;
acrylic and methacrylic acid polymers and esters;
poly(ortho ester)s; and
polyacetals.

Claims 10 through 12 divide those materials into narrower groups. A product using a polymer outside these groups could still potentially fall within claim 1 if the polymer satisfies claim 1’s functional language. It would not fall within claims 9 through 12 solely on that basis.

Pore-forming additives

Claim 13 covers broad classes, including:

water;
alkali-metal salts;
alkaline-earth-metal salts;
saccharides;
aliphatic polyols; and
aromatic polyols.

Claim 15 narrows the additive to polyethylene glycol, sorbitol, glucose, or mixtures. The additive must be pH-insensitive under claim 1. The claim therefore creates a technical distinction from pH-responsive coating systems that change permeability primarily because of environmental pH.

Wall dimensions and pore sizes

Claims 5 and 8 provide alternative dimensional limitations. The ranges are broad:

wall thickness: 20 to 500 microns under claim 5;
wall thickness: 1 to 1,000 microns under claim 8;
pore diameter: 10 angstroms to 25 microns under claim 5;
pore distribution: 5% to 95% of pores between 10 angstroms and 100 microns under claim 8.

A formulation may satisfy claim 1 without satisfying these dependent dimensional claims.

When did US Patent 4,880,631 expire?

US Patent 4,880,631 issued on November 14, 1989. For a US patent governed by the pre-1995 patent-term regime, the ordinary term was 17 years from issuance. On that basis, the patent expired on November 14, 2006. The patent is therefore no longer enforceable as a live US patent.

Event	Date or status
US patent issued	November 14, 1989
Ordinary pre-1995 term	17 years from issue
Calculated expiration	November 14, 2006
Current US enforceability	Expired
Current Paragraph IV threat from this patent	None
Current injunction risk based solely on this patent	None

The expiration analysis should be distinguished from any foreign counterpart. US expiration does not determine Canadian, European, Japanese, or other national rights. It also does not eliminate separate rights in later patents covering particular diltiazem formulations, dosage forms, manufacturing processes, or delivery devices.

What is the Orange Book status of US Patent 4,880,631?

US Patent 4,880,631 should not be treated as a current Orange Book barrier solely because it concerns diltiazem. The patent expired in 2006, and Orange Book listing is product-specific.

The FDA Orange Book generally identifies patents submitted by an NDA holder for an approved drug product. A patent involving a particular diltiazem L-malate osmotic device would require a corresponding approved product and an applicable patent submission. The existence of a patent in the USPTO record does not establish that it was listed for Cardizem, Cardizem CD, Tiazac, Dilacor XR, or another diltiazem product.

The principal regulatory conclusions are:

the patent is not a current patent-term obstacle to ANDA approval;
an expired patent cannot support a present Paragraph IV litigation claim;
a historical Orange Book listing, if any, would not create current exclusivity;
current diltiazem approval risk must be assessed against the patents listed for the specific reference listed drug.

FDA approval of generic diltiazem products has generally involved product-specific dosage forms and release profiles, not automatic authorization to practice every technical disclosure in this patent. FDA approval and patent freedom to operate are separate inquiries.[1]

Were there Paragraph IV challenges or patent litigation involving this patent?

No current Paragraph IV challenge can be maintained against an expired patent. Public patent litigation searches should distinguish this patent from later diltiazem patents and from litigation involving other Alza osmotic technologies.

A Paragraph IV certification would have been relevant only while the patent was listed and unexpired for an approved reference product. The statutory 30-month stay under Hatch-Waxman would also depend on timely NDA-holder litigation after receipt of a Paragraph IV notice.[2]

The legal exposure from this patent is now limited to historical issues, including:

whether a product marketed before expiration practiced the claims;
whether a license or settlement covered the patent;
whether damages were time-barred or otherwise available;
whether a later patent independently covered the same commercial product; and
whether prosecution history limited any historical claim construction.

How strong was the patent estate for this technology?

The patent had a technically coherent but commercially narrow estate.

Strengths

Claim 1 combined a defined drug salt with a specific osmotic excipient ratio.
The porous-wall limitations targeted a delivery architecture rather than merely a composition.
Functional permeability and reflection-coefficient limitations could capture multiple wall compositions.
Dependent claims covered broad families of polymers and pore-forming additives.
Claim 20 potentially reached delivery devices without requiring every claim 1 wall limitation.

Weaknesses

The drug was limited to diltiazem L-malate rather than diltiazem generally.
Sodium bitartrate had to fall within a defined relative-weight range.
Claim 1 required a pH-insensitive pore former and narrow functional wall parameters.
Many conventional controlled-release diltiazem products use diltiazem hydrochloride, not diltiazem L-malate.
The patent term ended before the modern wave of generic extended-release diltiazem litigation.
The claims did not by themselves cover every multiparticulate, reservoir, matrix, bead, capsule, or conventional coated-tablet design.

The patent was stronger against a deliberately copied osmotic-pump design using the specified salt and excipient ratio than against a conventional diltiazem hydrochloride extended-release formulation.

How does this patent compare with later diltiazem patents?

Issue	US 4,880,631	Later diltiazem product patents
Drug form	Diltiazem L-malate	Often diltiazem hydrochloride
Delivery system	Osmotic pump	Capsules, beads, pellets, matrices, coated particles, or other modified-release systems
Core limitation	Diltiazem plus sodium bitartrate	Often particle size, coating, release profile, or dosage-form structure
Wall limitation	Porous water-insoluble wall	May use polymers, membranes, or multiparticulate coatings
Patent status	Expired in 2006	Must be reviewed patent by patent
Orange Book significance	No current barrier from this patent	Product-specific
Biosimilar relevance	None	None for a small-molecule diltiazem product

Diltiazem is a small molecule. Biosimilar approval pathways do not apply. Competitive entry occurs through ANDAs, 505(b)(2) applications, or abbreviated pathways appropriate to the dosage form and reference product, not through biosimilar applications.

What generic-entry risks exist for diltiazem products?

The expired patent creates no present generic-entry risk. Current risk may arise from other patents covering:

extended-release release profiles;
multiparticulate or bead formulations;
capsule or tablet architecture;
coating composition;
manufacturing processes;
crystalline or salt forms;
combination products;
labeling and method-of-use restrictions; and
patents listed against a specific reference listed drug.

A generic applicant pursuing an osmotic diltiazem product would still need to evaluate whether its design practices later, unexpired patents. It would not need to clear US 4,880,631 as a live patent.

A product using diltiazem hydrochloride, a non-osmotic matrix, or a delivery system without sodium bitartrate would have substantial design-distance from the literal scope of claim 1. Claim 20 requires a closer analysis because it lacks the expressly recited wall and osmotic-pump limitations.

Does US 4,880,631 create manufacturing or licensing barriers?

It does not create a current US manufacturing barrier because the patent has expired. During its term, the principal manufacturing risk would have involved:

preparation of diltiazem L-malate;
blending the drug with sodium bitartrate in the claimed ratio;
coating or forming a water-insoluble porous wall;
controlling wall permeability and reflection coefficient;
maintaining pore-former concentration during processing; and
reproducing the claimed wall thickness and pore distribution.

Historical licensing may still matter for chain-of-title, royalty, settlement, or archival diligence. The patent was associated with osmotic-delivery technology of the type developed and commercialized by Alza, but a current license to this expired US patent is not required to practice the expired US claims.

Key Takeaways

US Patent 4,880,631 is directed to a diltiazem L-malate osmotic pump.
Claim 1 requires diltiazem L-malate, sodium bitartrate at 80% to 150% by weight, and a porous water-insoluble wall with specified functional properties.
Claim 20 is a separate admixture claim and may be broader than claim 1 because it does not expressly require the full porous-wall structure.
Claims 2 through 19 narrow dosage, wall, polymer, pore-former, additive, and combination-product features.
The patent issued on November 14, 1989, and its ordinary US term expired on November 14, 2006.
It is not a current US patent barrier, Paragraph IV obstacle, or biosimilar issue.
Orange Book significance depends on product-specific listing history and does not follow automatically from the patent record.
Generic and 505(b)(2) applicants must focus on later, unexpired patents covering the relevant diltiazem reference product and dosage form.
The patent’s strongest historical coverage was against a copied diltiazem L-malate osmotic pump using sodium bitartrate and a porous membrane.

FAQs About US Patent 4,880,631

Can a product using diltiazem hydrochloride infringe US 4,880,631?

It would not literally satisfy the diltiazem L-malate limitation. Historical doctrine-of-equivalents issues would require a separate analysis, but the patent is expired and cannot create current US infringement liability.

Does claim 20 cover any controlled-release diltiazem formulation?

No. Claim 20 requires diltiazem L-malate, sodium bitartrate at the specified ratio, and an admixture in a drug-delivery device for controlled release. It does not cover all diltiazem formulations.

Is sodium bitartrate a required ingredient in claim 1?

Yes. Claim 1 requires sodium bitartrate at 80% to 150% by weight relative to diltiazem L-malate.

Is US 4,880,631 relevant to biosimilar approval?

No. Diltiazem is a small-molecule active ingredient, and biosimilar procedures do not apply.

Can this patent block a generic diltiazem ANDA today?

No. The patent expired in 2006. A generic applicant must instead assess current Orange Book-listed patents and other unexpired rights for the applicable reference product.

References

U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. FDA.
U.S. Congress. (1984). Drug Price Competition and Patent Term Restoration Act of 1984, Pub. L. No. 98-417, 98 Stat. 1585.
United States Patent and Trademark Office. (1989). U.S. Patent No. 4,880,631: Osmotic device for delivering diltiazem L-malate. USPTO.
U.S. Food and Drug Administration. (2024). Orange Book: Approved drug products with therapeutic equivalence evaluations. FDA.
U.S. Code, 35 U.S.C. §§ 154, 156, 271(e), 282.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	73322	⤷ Start Trial
Australia	2277388	⤷ Start Trial
Australia	604564	⤷ Start Trial
Canada	1320885	⤷ Start Trial
Germany	3869032	⤷ Start Trial
Denmark	529188	⤷ Start Trial
European Patent Office	0309051	⤷ Start Trial
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Details for Patent: 4,880,631

Summary for Patent: 4,880,631