United States Patent 4,173,626: Indomethacin Sustained-Release Formulation, Claim Scope, Expiration, and Patent Landscape

U.S. Patent No. 4,173,626 covers a capsule containing immediate-release and sustained-release indomethacin pellets. The central limitation is a multiparticulate dosage form in which approximately 35% of the indomethacin is released rapidly from uncoated pellets and approximately 65% is released more slowly from polyvinyl acetate-coated pellets. The patent issued on November 6, 1979, and its ordinary U.S. patent term expired on November 6, 1996. The claims therefore do not create a current U.S. patent barrier to generic indomethacin extended-release products.[1][2]

The patent remains relevant for historical product identification, freedom-to-operate analysis, Orange Book review, and comparison with later indomethacin formulation patents. It does not create current biosimilar risk because indomethacin is a small-molecule drug, not a biologic.

What does U.S. Patent 4,173,626 cover?

U.S. Patent 4,173,626 covers a sustained-release pharmaceutical formulation of indomethacin in capsule form. The claimed formulation uses two pellet populations:

Claim element	Required feature
Active ingredient	Indomethacin
Dosage form	Capsule unit dosage form
Total indomethacin	25 to 150 mg
Pellet size	500 to 1,500 microns
Immediate-release fraction	Uncoated pellets containing 5 to 50 mg indomethacin
Immediate-release proportion	About 35% of total indomethacin
Sustained-release fraction	Coated pellets containing 15 to 145 mg indomethacin
Sustained-release proportion	About 65% of total indomethacin
Coating	Polyvinyl acetate as a slow-dissolving material
Clinical function	Rapid initial plasma elevation followed by prolonged plasma levels

The patent is directed to a multiparticulate delivery system rather than a single monolithic tablet or a conventional powder-filled capsule. The uncoated pellets provide the loading dose. The coated pellets provide the maintenance component.

The claim is structured as a “comprising” claim. That generally permits additional formulation ingredients or processing components unless they remove a required limitation. A formulation can therefore contain excipients beyond those expressly identified in claim 1, but it must still contain the claimed pellet architecture and release fractions.

How does claim 1 define the protected indomethacin formulation?

Claim 1 has both structural and functional limitations.

Structural limitations

The formulation must contain:

A capsule.
Indomethacin-containing pellets.
Pellets within the stated 500-to-1,500-micron size range.
An uncoated pellet population.
A coated pellet population.
Polyvinyl acetate coating on the sustained-release population.
The specified broad dose ranges.

A product that uses ethylcellulose, methacrylate polymers, cellulose acetate, lipid coatings, or another release-controlling material may avoid literal infringement of the polyvinyl acetate limitation. The result would depend on the complete claim construction and any doctrine-of-equivalents analysis.

Functional limitations

Claim 1 also requires the formulation to provide:

Rapid elevation of plasma indomethacin levels from the uncoated pellets.
Prolonged plasma levels from the coated pellets.
Clinical effectiveness.

These limitations could create claim-construction questions. “Rapid,” “prolonged,” and “clinically effective” are not expressed through numerical dissolution or pharmacokinetic thresholds in the supplied claim text. A court would likely evaluate the intrinsic patent disclosure, prosecution history, and technical meaning at the relevant filing date.

The functional language does not eliminate the structural requirements. A formulation that produces prolonged plasma levels but lacks polyvinyl acetate-coated pellets would not ordinarily satisfy claim 1 literally.

What dose and release ranges are covered?

The claimed total dose is 25 to 150 mg. The uncoated fraction may contain 5 to 50 mg, and the coated fraction may contain 15 to 145 mg.

The stated release allocation is approximately:

Fraction	Claimed amount	Stated role
Uncoated pellets	5 to 50 mg	About 35% immediate release
Polyvinyl acetate-coated pellets	15 to 145 mg	About 65% sustained release
Total	25 to 150 mg	Prolonged plasma exposure

The numerical subranges do not mathematically require an exact 35:65 ratio in every combination. For example, 5 mg immediate-release drug and 145 mg sustained-release drug produce a materially different ratio from 50 mg and 15 mg. The word “about” gives additional flexibility, but its scope would depend on the specification, prosecution record, and technical evidence.

A commercial 75-mg capsule could fall within the total-dose range, but dose alone is insufficient for infringement. The product would also need the claimed pellet size, immediate-release and sustained-release fractions, and polyvinyl acetate coating.

What does claim 2 add to the patent scope?

Claim 2 depends on claim 1 and adds non-medicated pellets to adjust the capsule fill volume.

This limitation addresses manufacturing and dosage-form uniformity. In a multiparticulate capsule, the amount of medicated pellets may not fill the capsule consistently or may produce excessive free volume. Non-medicated pellets can provide a controlled diluent volume without adding additional indomethacin.

Claim 2 is narrower than claim 1. A formulation that satisfies all elements of claim 1 but does not include non-medicated pellets may still implicate claim 1 while avoiding claim 2.

The claim does not appear to require a particular composition, size, coating, or amount for the non-medicated pellets based on the supplied text. The limitation is their presence and their function in achieving the adjusted fill volume.

What formulation ingredients are protected by claim 3?

Claim 3 narrows component (A), the uncoated immediate-release pellets, to a composition containing:

Ingredient	Claimed range by weight
Indomethacin	10% to 35%
Confectioner’s sugar	20% to 40%
Hydroxypropylmethylcellulose	3% to 15%
Corn starch	3% to 15%
Microcrystalline cellulose	15% to 25%

Component (B) must consist of component (A) pellets coated with the claimed slow-dissolving material, namely polyvinyl acetate.

The use of “comprising” means the listed ingredients are generally open-ended. Additional excipients may be present unless the claim or specification supports a narrower construction. The percentages also create an important technical issue: the listed ranges can sum to less than or more than 100%. That suggests the claim uses component-relative weight percentages rather than a rigid requirement that every listed minimum and maximum be selected simultaneously as a complete formulation.

Claim 3 is materially narrower and more vulnerable to design-around than claim 1. A competitor could seek to alter the pellet matrix by:

Replacing confectioner’s sugar with lactose, mannitol, or another carrier.
Removing or materially reducing hydroxypropylmethylcellulose.
Replacing corn starch with pregelatinized starch or another disintegrant.
Replacing microcrystalline cellulose with another pellet-forming excipient.
Changing the active-load percentage.
Using a different sustained-release coating.

The patent’s strongest historical protection is therefore claim 1’s combined pellet architecture. Claim 3 provides more specific composition coverage but also supplies more potential noninfringement positions.

When did U.S. Patent 4,173,626 expire?

The patent issued on November 6, 1979. For a U.S. patent governed by the pre-1995 term regime, the ordinary term was 17 years from issuance. On that basis, U.S. Patent 4,173,626 expired on November 6, 1996.[1][3]

Event	Date
Patent issue	November 6, 1979
Ordinary 17-year expiration	November 6, 1996
Current status	Expired
Current blocking effect	None for U.S. manufacture, sale, or approval

Patent term adjustment under current law does not generally extend a pre-1995 patent beyond the applicable statutory term. Patent-term extension for regulatory review also would not ordinarily be expected to create a current right for this patent, and the patent is treated as expired in the historical Orange Book context.[2][3]

What was the FDA and Orange Book status of the patent?

Indomethacin is an FDA-approved nonsteroidal anti-inflammatory drug. Immediate-release indomethacin products have historically been marketed as capsules, oral suspensions, and suppositories. Sustained-release indomethacin was marketed in capsule form, including the Indocin SR product category.[4]

The Orange Book historically provided patent and exclusivity information for approved drug products. The expiration of U.S. Patent 4,173,626 means that any former Orange Book listing no longer creates a current patent-based delay to an abbreviated new drug application.[2]

Regulatory issue	Assessment
Active ingredient	Indomethacin
Product category	Small-molecule NSAID
FDA pathway for generics	ANDA under section 505(j)
Biosimilar pathway	Not applicable
Historical patent relevance	Sustained-release pellet formulation
Current patent blockage	None from U.S. 4,173,626
Current exclusivity	No patent exclusivity from this patent

An ANDA applicant seeking an extended-release indomethacin product would still need to address FDA requirements for pharmaceutical equivalence, bioequivalence, labeling, inactive ingredients, dissolution, and manufacturing controls. Patent expiration does not remove those regulatory requirements.[2][4]

Were Paragraph IV challenges or litigation associated with this patent?

A Paragraph IV certification is relevant only while a listed patent remains unexpired and is asserted against an ANDA applicant. Because U.S. Patent 4,173,626 expired in 1996, it cannot currently support a new Paragraph IV litigation strategy or a 30-month stay under the Hatch-Waxman framework.[5]

The patent record supplied here does not establish a current infringement case, active ANDA litigation, or enforceable settlement restriction associated with this patent. Any historical Paragraph IV dispute involving an indomethacin sustained-release product would have been time-limited by the patent’s 1996 expiration.

No continuing settlement covenant, launch restriction, or license obligation can be inferred from the expired patent itself. Such obligations would require a separate agreement.

How strong was the patent estate for this formulation?

The patent had moderate historical strength against products that copied the specific two-population pellet design. Its strongest features were the combination of:

Uncoated and coated pellets in one capsule.
A defined immediate-release and sustained-release allocation.
Polyvinyl acetate as the sustained-release coating.
A pellet-size range.
Specific indomethacin dose ranges.

Its weaker features included:

Broad functional language.
The imprecise term “about” for the release allocation.
No explicit dissolution profile in the supplied claims.
No numeric plasma-concentration or pharmacokinetic threshold.
Potential design-around options using different coating polymers or pellet matrices.
A claim architecture dependent on proving the internal composition of a competitor’s capsule.

The patent could have been difficult to evaluate through finished-product testing alone if the coating polymer and pellet composition were not disclosed. Discovery, reverse engineering, regulatory filings, and manufacturing records would have been important in any historical enforcement action.

How does this patent compare with later indomethacin patents?

U.S. Patent 4,173,626 is a formulation patent, not a compound patent. Indomethacin itself was discovered and commercialized before this patent, so the patent did not control the active ingredient generally.

Patent category	Covered subject matter	Relevance today
Compound patent	Indomethacin molecule	Expired
Claim 4,173,626	Immediate-release and polyvinyl acetate-coated pellets	Expired
Method-of-use patent	Treatment of an indication or patient group	Must be reviewed separately
Formulation patent	Alternative release system, coating, tablet, capsule, or particle design	Depends on each patent’s term
Manufacturing patent	Pelletization, coating, drying, or process controls	Depends on each patent’s term

A current freedom-to-operate review should not stop at U.S. Patent 4,173,626. Later patents could have claimed different extended-release technologies, controlled-release coatings, manufacturing methods, or dosing regimens. Those rights would need separate family-level review in the United States and relevant foreign jurisdictions.

What generic launch risks exist for indomethacin extended-release products?

The expired patent removes the principal historical patent risk associated with the claimed pellet design. Remaining launch risks are primarily regulatory, technical, and commercial:

Demonstrating bioequivalence to the applicable reference product.
Matching the required extended-release performance.
Establishing acceptable in-vitro dissolution profiles.
Controlling pellet size, coating uniformity, and capsule fill weight.
Confirming inactive-ingredient compatibility.
Determining whether any later formulation or method-of-use patent remains active.
Managing limited commercial demand for an older NSAID product.

Generic competition may target immediate-release indomethacin rather than reproduce the patented pellet system. A technically different extended-release formulation could avoid the expired patent entirely, subject to any later patent rights.

What is the geographic coverage of U.S. Patent 4,173,626?

The patent provided U.S. rights only. It did not automatically protect the formulation in Europe, Canada, Japan, or other markets. Foreign protection would require corresponding national patents or regional rights with separate filing dates, claim scopes, and expiration dates.

Because the U.S. patent expired in 1996, it provides no current U.S. manufacturing, importation, sale, or offer-for-sale exclusion. Foreign markets require independent patent-family analysis.

Key Takeaways

U.S. Patent 4,173,626 claims an indomethacin capsule containing uncoated immediate-release pellets and polyvinyl acetate-coated sustained-release pellets.
Claim 1 requires approximately 35% immediate release and 65% sustained release, with total indomethacin of 25 to 150 mg.
Claim 2 adds non-medicated pellets for capsule fill-volume adjustment.
Claim 3 narrows the uncoated pellets to specified ranges of indomethacin, confectioner’s sugar, hydroxypropylmethylcellulose, corn starch, and microcrystalline cellulose.
The patent issued November 6, 1979, and expired November 6, 1996.
The patent creates no current U.S. patent barrier and cannot support a new Paragraph IV stay.
No biosimilar analysis applies because indomethacin is a small molecule.
Current launch analysis should focus on later formulation, manufacturing, method-of-use patents, FDA bioequivalence, and commercial viability.

FAQs About U.S. Patent 4,173,626

Can a generic company market a 75-mg indomethacin extended-release capsule today?

The expired patent does not prevent launch. The applicant must still satisfy FDA approval, bioequivalence, manufacturing, labeling, and any later active patent requirements.

Does using a different coating polymer avoid claim 1?

It may avoid literal infringement of the polyvinyl acetate limitation, but the complete formulation and any doctrine-of-equivalents issue would require analysis under the applicable patent law.

Does claim 3 require the ingredients to total exactly 100%?

The supplied claim language uses “comprising” and lists ranges by weight. It does not expressly require every listed component to be present at a selected amount that totals exactly 100%.

Is Indocin SR a biologic product?

No. Indocin SR is an indomethacin small-molecule oral dosage form. Generic approval proceeds through the ANDA pathway, not the biosimilar pathway.

Can the expired patent still affect a foreign launch?

No direct U.S. effect exists, but foreign counterparts, national patents, supplementary protection rights, or later patents must be reviewed separately in each target jurisdiction.

References

United States Patent and Trademark Office. (1979). U.S. Patent No. 4,173,626.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
35 U.S.C. § 154. Patent term and rights.
U.S. Food and Drug Administration. (n.d.). Indomethacin prescribing information and approved labeling.
21 U.S.C. § 355(j). Abbreviated applications and patent certifications.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Bulgaria	60753	⤷ Start Trial
Canada	1149742	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 4,173,626

Summary for Patent: 4,173,626