United States Patent 4,916,163: Glyburide Formulation Claims, Expiration, and Patent Landscape

U.S. Patent 4,916,163 protected a pharmaceutical composition containing micronized glyburide with spray-dried lactose as the predominant excipient. The independent claim required spray-dried lactose to constitute at least approximately 70% by weight of the final dosage unit. The patent issued on April 10, 1990, and its ordinary 17-year term expired on April 10, 2007. The claims no longer create an enforceable U.S. patent barrier to generic glyburide products.

The patent was formulation-specific rather than molecule-specific. It did not broadly protect glyburide, micronized glyburide as an active ingredient, or all glyburide tablets. Its scope depended on the combination of micronized glyburide, spray-dried lactose, and the claimed quantitative threshold.

What did U.S. Patent 4,916,163 protect?

The patent covered unit-dose antidiabetic pharmaceutical compositions containing micronized glyburide and one or more pharmaceutically acceptable excipients. The central formulation limitation was spray-dried lactose at not less than about 70% by weight of the finished composition.

Claim	Main limitation	Scope
1	Micronized glyburide; unit-dose pharmaceutical composition; spray-dried lactose as the preponderant excipient; at least about 70% by weight of the final composition	Independent composition claim
2	Claim 1 plus micronized glyburide having a surface area of about 5 m²/g	Particle-surface-area limitation
3	Claim 1 plus a glidant, lubricant and disintegrant	Functional excipient-category limitation
4	Claim 1 plus corn starch, silicon dioxide and magnesium stearate	Specific excipient combination

The claims are composition claims. They do not expressly claim a manufacturing process, a method of treating diabetes, a method of reducing glyburide particle size, or a particular tablet strength.

How should claim 1 be construed?

Claim 1 has five principal limitations:

The product must be a pharmaceutical composition.
The composition must be a unit dose.
The active ingredient must be micronized glyburide.
The composition must contain one or more pharmaceutically acceptable excipients.
Spray-dried lactose must be the preponderant excipient and must comprise approximately 70% or more of the final composition by weight.

The phrase "preponderant excipient" reinforces the quantitative limitation. A formulation could contain several excipients, but spray-dried lactose must remain the dominant excipient and must meet the approximately 70% threshold.

The claim uses "about," which introduces a potential claim-construction issue around the 70% boundary. In an infringement dispute, the relevant question would be whether a formulation containing slightly less than 70% still falls within the ordinary meaning of "about 70%" in view of the specification, prosecution history and technical evidence. A product with materially less than 70% spray-dried lactose would present a stronger noninfringement position.

The claim does not require:

A particular glyburide dose.
A particular tablet weight.
A particular glyburide particle-size distribution.
A particular dissolution profile.
A particular brand or manufacturer.
Corn starch, silicon dioxide or magnesium stearate.
A specific diabetes indication.

What does "micronized glyburide" add to the scope?

"Micronized glyburide" limits claim 1 to glyburide processed into substantially smaller particles than conventional coarse drug substance. The claim text does not provide a numerical particle-size cutoff.

That omission creates a technical claim-construction issue. The term could be interpreted using the patent specification, ordinary pharmaceutical usage, manufacturing records and expert evidence. Claims 2 adds a more specific surface-area limitation of approximately 5 m²/g, but claim 1 is not expressly limited to that value.

Claim 2 is narrower than claim 1 because it requires both:

The composition of claim 1; and
Micronized glyburide with a surface area of about 5 m²/g.

A product using micronized glyburide with a materially different surface area could potentially avoid claim 2 while still implicating claim 1 if all other limitations were satisfied.

What formulations are protected by claims 3 and 4?

Claims 3 and 4 narrow claim 1 by adding excipient limitations.

Claim 3: functional excipient categories

Claim 3 requires the excipients to comprise:

A glidant;
A lubricant; and
A disintegrant.

The claim does not identify particular chemical materials. Depending on the specification and ordinary pharmaceutical usage, materials may perform more than one function. Silicon dioxide, for example, can operate as a glidant, while magnesium stearate is commonly used as a lubricant and starch may function as a disintegrant.

Claim 3 therefore has broader excipient coverage than claim 4 but may create more interpretation around whether a particular material satisfies a claimed functional category.

Claim 4: specific excipient combination

Claim 4 requires:

Corn starch;
Silicon dioxide; and
Magnesium stearate.

Claim 4 does not state the quantities of these three excipients. It also does not expressly state that each must perform a specific function, although the listed materials correspond broadly to the functional categories in claim 3.

A composition containing all three materials, micronized glyburide and at least approximately 70% spray-dried lactose would fall within the literal scope of claim 4 if the other claim 1 limitations were met.

How many patents covered the glyburide formulation?

Patent 4,916,163 appears to have been the principal U.S. patent directed to the spray-dried-lactose formulation described in the claims supplied. Its claim set is narrow compared with a conventional active-ingredient patent because it focuses on dosage-form composition and excipient selection.

The relevant patent categories are:

Patent category	Relevance to Patent 4,916,163
Glyburide compound patents	Protect the chemical entity or chemical class, not necessarily this formulation
Micronization or particle-size patents	May cover drug-substance properties or processing, but are distinct from the claimed lactose composition
Formulation patents	Most relevant category; includes excipient ratios, dissolution, stability or dosage-form architecture
Method-of-use patents	Not claimed by Patent 4,916,163
Combination-product patents	May cover glyburide with metformin or other agents, but are separate from the single-agent composition claims
Manufacturing-process patents	Not claimed by the supplied claims
Packaging or device patents	Outside the supplied claim scope

A complete freedom-to-operate review would require a family-level search of issued, expired, abandoned and terminally disclaimed U.S. patents covering glyburide particle engineering, tablet manufacture, excipient selection and combination products. The supplied claims alone do not establish that every later glyburide formulation patent had the same scope.

When did U.S. Patent 4,916,163 lose exclusivity?

The patent issued April 10, 1990. For a pre-June 8, 1995 U.S. application, the ordinary patent term was generally 17 years from issuance, subject to terminal disclaimers and other adjustments under the law then applicable.

Event	Date or status
Patent issuance	April 10, 1990
Ordinary 17-year expiration	April 10, 2007
Current enforceability	Expired
Current ability to block generic launch	None based on this patent
Patent-term extension relevance	No current extension is identified for this formulation patent

The expiration date means that a current manufacturer does not need a license from the patent owner to practice the claimed formulation in the United States. It also means that a present-day product review should focus on later patents, regulatory requirements, trade secrets and manufacturing know-how rather than Patent 4,916,163.

What was the Orange Book status of Patent 4,916,163?

The Orange Book lists patents submitted by sponsors and accepted by FDA for approved drug products. A patent’s presence or absence in the current Orange Book does not change whether an expired patent once existed, but it affects abbreviated new drug application certification and patent-notice procedures.

Patent 4,916,163 is not a current enforceable Orange Book barrier for glyburide products. Any historical listing associated with a glyburide product would no longer create a live Hatch-Waxman stay or launch block after expiration. FDA’s Orange Book framework applies to listed patents connected to approved drug products, while patent expiration is determined under patent law and the official patent record.[2]

The key regulatory distinction is:

An expired formulation patent can remain historically relevant to product development and litigation analysis.
It cannot support a current Paragraph IV litigation stay or injunction.
A later patent may still affect a generic applicant if it is properly listed and unexpired.

Did Patent 4,916,163 create Paragraph IV risk?

During its term, an abbreviated new drug applicant seeking approval for a glyburide product potentially could have addressed the patent through a patent certification. A Paragraph IV certification would assert that the patent was invalid, unenforceable or would not be infringed by the proposed product.[3]

The practical risk profile was formulation-dependent:

Proposed generic formulation	Historical risk under claim 1
Micronized glyburide with at least approximately 70% spray-dried lactose	High literal-infringement exposure
Micronized glyburide with less than approximately 70% spray-dried lactose	Lower risk, subject to "about" construction
Glyburide with ordinary, nonmicronized particle characteristics	Lower risk
Micronized glyburide with a different dominant excipient	Lower risk
Product using spray-dried lactose but not as the preponderant excipient	Lower risk
Product containing the claim 4 excipients and meeting all claim 1 limitations	Claim 4 exposure
Product with a different dosage form or non-unit-dose presentation	Potential claim 1 defense, depending on product presentation

Today, Paragraph IV risk from this patent is effectively zero because the patent expired in 2007. A current applicant would evaluate later-listed patents, not the expired claims of Patent 4,916,163.

Which companies challenged glyburide patents?

Glyburide has been marketed in the United States through multiple branded and generic products, including products associated with Micronase and DiaBeta. Glyburide also has been used in combination products such as glyburide-metformin products.

The supplied patent information does not establish a particular Paragraph IV challenger, settlement agreement or final judgment involving Patent 4,916,163. Those issues require a case-specific review of FDA patent certifications, federal court dockets, ANDA litigation records and historical Orange Book editions. No current litigation consequence follows from the expired claims.

How strong was the patent estate?

The estate was technically narrow but commercially relevant during its term.

Strengths

Claim 1 covered the central formulation architecture.
The 70% threshold was objective enough to support product testing and formulation comparison.
The use of spray-dried lactose could be identified through composition records and manufacturing documentation.
Dependent claims addressed both particle surface area and standard tablet excipient systems.
The claims did not require a particular brand, tablet strength or therapeutic indication.

Limitations

The patent did not cover glyburide as a chemical entity.
It did not cover all micronized glyburide formulations.
It did not claim a method of treating diabetes.
It did not claim a manufacturing process for spray-dried lactose or micronized glyburide.
A generic manufacturer could potentially design around the 70% threshold or use a different dominant excipient.
The term "about" could create uncertainty near the 70% boundary.
The patent term expired before current generic development activity in this product class.

Patent 4,916,163 was therefore a formulation patent with meaningful blocking value for a defined product design, not a broad glyburide exclusivity patent.

What generic launch scenarios existed?

During the patent term, generic manufacturers had several design-around options:

Use less than approximately 70% spray-dried lactose.
Use a different lactose grade or a different dominant filler, subject to the interpretation of "spray-dried lactose."
Use nonmicronized or differently processed glyburide.
Use a formulation that omits one or more excipient categories required by claims 3 and 4.
Use a different dosage form or product architecture.
Challenge the patent through a Paragraph IV certification.

After April 10, 2007, the patent no longer constrained any of these launch strategies.

Did the patent create biosimilar risk?

No. Glyburide is a chemically synthesized small-molecule drug. It is regulated through the generic-drug framework rather than the biosimilar pathway under the Public Health Service Act.

The relevant approval route is an ANDA demonstrating pharmaceutical equivalence and bioequivalence to a reference listed drug, subject to applicable FDA requirements. Biosimilar interchangeability, reference-biologic exclusivity and biologics patent dance procedures do not apply to this patent.[4]

What manufacturing and intellectual-property barriers remain?

Patent 4,916,163 does not create a current manufacturing barrier. A company can manufacture a glyburide product using spray-dried lactose without licensing this expired patent.

Potential barriers may remain in other areas:

Supplier qualification for micronized glyburide.
Particle-size control and surface-area reproducibility.
Blend uniformity at low glyburide loading.
Tablet dissolution and content uniformity.
Control of electrostatic behavior and powder flow.
Stability data for the selected lactose grade.
Regulatory compliance for the reference-product comparison.
Later patents covering combination products, modified release, manufacturing processes or specific formulations.
Trade secrets involving milling, blending, compression and scale-up.

These are commercial and regulatory issues, not continuing rights under Patent 4,916,163.

How does Patent 4,916,163 compare with broader drug patents?

Feature	Patent 4,916,163	API patent	Method-of-use patent	Process patent
Protects glyburide molecule	No	Usually yes	No	No
Protects a formulation	Yes	Usually no	Sometimes indirectly	Sometimes
Requires spray-dried lactose	Yes	No	No	No
Requires approximately 70% excipient threshold	Yes	No	No	No
Covers treatment of diabetes	No	No	Yes	No
Covers manufacturing steps	No	No	No	Yes
Current enforceability	No, expired	Depends on patent	Depends on patent	Depends on patent

Key Takeaways

Patent 4,916,163 protected a narrow micronized glyburide tablet formulation.
Claim 1 required spray-dried lactose at approximately 70% or more of the final composition by weight.
Claim 2 added a glyburide surface area of approximately 5 m²/g.
Claim 3 required a glidant, lubricant and disintegrant.
Claim 4 required corn starch, silicon dioxide and magnesium stearate.
The patent did not protect glyburide generally, all micronized glyburide products or diabetes treatment methods.
The patent issued April 10, 1990, and its ordinary term expired April 10, 2007.
It creates no current U.S. generic-launch, Orange Book or Paragraph IV barrier.
Glyburide is a small molecule, so biosimilar analysis is not applicable.
Current freedom-to-operate analysis must focus on later formulation, combination-product, process and method-of-use patents.

FAQs About U.S. Patent 4,916,163

Can a company sell a glyburide tablet containing spray-dried lactose today?

Yes. Patent 4,916,163 expired in 2007. A company must still satisfy FDA requirements and avoid any later unexpired patent, but this patent does not require a license.

Does the patent cover micronized glyburide with any excipient?

No. The composition must include spray-dried lactose as the preponderant excipient at approximately 70% or more by weight of the final composition.

Is claim 2 limited to glyburide with exactly 5 m²/g surface area?

No. The term "about" prevents an automatic exact-value reading. The enforceable range would depend on the intrinsic patent record and technical evidence, but claim 2 is narrower than claim 1.

Does claim 4 require a particular amount of corn starch, silicon dioxide or magnesium stearate?

The supplied claim does not state specific amounts for those three excipients. It requires their presence in a composition that also satisfies claim 1.

Is a glyburide-metformin product covered by Patent 4,916,163?

Not necessarily. The supplied claims are directed to a micronized glyburide composition and do not expressly require or exclude metformin. A combination product would need to satisfy every limitation of the relevant claim, while separate patents could apply to glyburide-metformin formulations.

References

United States Patent No. 4,916,163, claims 1-4 (issued Apr. 10, 1990).
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations (Orange Book).
U.S. Food and Drug Administration. (2015). ANDA submissions: Amendments and prior approval supplements under GDUFA.
U.S. Food and Drug Administration. (2023). Abbreviated new drug application process for generic drugs.

Details for Patent: 4,916,163

Summary for Patent: 4,916,163