United States Patent 5,338,732: Megestrol Acetate Oral Suspension Patent Scope and Landscape

U.S. Patent No. 5,338,732 covers an oral liquid suspension containing micronized megestrol acetate, polysorbate, polyethylene glycol and, in one claim, a specific 40 mg/mL formulation. The patent is directed to physical stability and redispersibility of megestrol acetate suspensions rather than to megestrol acetate itself, its therapeutic use, or the manufacturing process in general. The patent issued on August 16, 1994, and its original 17-year patent term expired on August 16, 2011, subject to any applicable patent-term adjustment or extension shown in the official patent records. It is no longer an enforceable barrier to generic formulation development. [1]

What patents protect megestrol acetate oral suspension?

U.S. Patent 5,338,732 protects specified liquid compositions of micronized megestrol acetate that form a stable flocculated suspension in water. The central formulation includes:

Component	Claim 1 range	Preferred or specific range
Micronized megestrol acetate	15-150 mg/mL	20-120 mg/mL; 40 mg/mL
Polysorbate	0.005%-0.015% w/v	0.01% w/v
Polyethylene glycol	Greater than 5% w/v	5%-30%; 12%-24%; 20%
Suspension state	Stable flocculated suspension in water	Required by the claims
Dosage form	Oral pharmaceutical composition	Required by the claims

The patent's commercial significance came from its relationship to megestrol acetate oral suspensions, particularly products historically marketed as Megace Oral Suspension. Megestrol acetate is a progestational agent used in appetite stimulation and the treatment of anorexia or significant weight loss associated with certain disease states. The patent does not claim every megestrol acetate liquid, every oral megestrol acetate product, or every suspension containing a surfactant.

What is the claim scope of U.S. Patent 5,338,732?

The claims are composition claims with concentration limitations and a physical-performance limitation. A potentially infringing product would need to satisfy every limitation of at least one asserted claim.

Claim 1: broadest independent composition claim

Claim 1 requires all of the following:

An oral pharmaceutical composition.
Micronized megestrol acetate.
Megestrol acetate concentration of 15 to 150 mg/mL.
Polysorbate concentration of 0.005% to 0.015% w/v.
Polyethylene glycol concentration greater than 5% w/v.
A stable flocculated suspension in water.

The numerical ranges are material. A formulation containing 10 mg/mL or 200 mg/mL megestrol acetate would fall outside the express concentration range of claim 1. A formulation using 0.02% polysorbate would also fall outside the polysorbate range. The same applies to a formulation containing 5% or less polyethylene glycol, although claim 5 introduces a drafting issue discussed below.

The phrase "stable flocculated suspension in water" limits the claim beyond the ingredient list. A formulation must be a suspension with the claimed physical behavior. A clear solution, a deflocculated suspension, or a formulation that rapidly sediments into a hard cake would present a stronger non-infringement position, subject to claim construction and testing evidence.

Claims 2 and 3: megestrol acetate concentration

Claim 2 narrows the megestrol acetate range to 20-120 mg/mL. Claim 3 specifies 40 mg/mL. These claims are commercially important because 40 mg/mL is the concentration associated with conventional Megace oral suspension products.

A 40 mg/mL formulation can satisfy claim 3 only if it also contains the polysorbate, polyethylene glycol and stable-flocculation characteristics required by claim 1. The 40 mg/mL concentration alone does not establish infringement.

Claims 4 and 8: polysorbate

Claim 4 specifies polysorbate 80. Claim 8 specifies a polysorbate concentration of 0.01% w/v.

These limitations identify the preferred surfactant and concentration but do not independently claim polysorbate 80 in all megestrol acetate products. A formulation using polysorbate 80 at 0.01% w/v would remain within the claim only if the other claim 1 limitations were met.

A formulation using a different surfactant, such as polysorbate 20, may avoid claims 4 and 8, but it could still implicate claim 1 if the selected material qualifies as "polysorbate" and all other limitations are present.

Claims 5 through 7: polyethylene glycol

Claim 5 recites polyethylene glycol at 5% to 30% w/v. Claim 6 narrows that range to 12%-24% w/v, and claim 7 specifies 20% w/v.

The preferred composition therefore centers on polyethylene glycol at 20% w/v. The patent identifies polyethylene glycol 1450 in claim 10, but claims 1 and 5-8 do not expressly limit the polyethylene glycol to a particular molecular weight unless that limitation is incorporated through the specification or claim construction.

A formulation with PEG 1450 at 20% w/v is within the express concentration selected by claim 7, provided that the other limitations are met.

Claim 9: conventional excipients

Claim 9 adds buffering, sweetening and flavoring agents. It protects a more commercially usable oral product rather than a basic suspension vehicle alone.

The claim does not appear to require a particular buffer, sweetener or flavor. The specification and claim language would control whether the terms are construed broadly or whether specific disclosed excipients are required. The presence of these excipients does not remove the need to satisfy claim 1.

Claim 10: exact formulation claim

Claim 10 recites the following formulation:

Ingredient	Amount, % w/v
Megestrol acetate	4.00%
Polyethylene glycol 1450	20.00%
Polysorbate 80	0.01%
Xanthan gum	0.20%
Sodium benzoate	0.20%
Citric acid	0.244%
Sodium citrate	0.015%
Sucrose	5.00%
Lemon-lime flavor	0.091%
Purified water	Remainder

Four percent w/v megestrol acetate equals 40 mg/mL. Claim 10 therefore captures the labeled-strength formulation with PEG 1450, polysorbate 80, xanthan gum, preservative, buffer, sweetener and flavor.

Because claim 10 is highly specific, a product that varies one or more ingredients or concentrations may avoid literal infringement. Equivalence arguments would depend on the nature of the variation, prosecution history, claim construction and technical evidence.

How strong is the patent estate for megestrol acetate oral suspension?

The patent was technically narrow but commercially relevant during its term. Its strength came from the combination of:

A clinically used 40 mg/mL strength.
A defined low level of polysorbate.
High polyethylene glycol content.
A flocculated, physically stable suspension.
A commercial excipient profile in claim 10.

Its limitations were equally clear. The patent did not cover:

The megestrol acetate molecule itself.
All pharmaceutical uses of megestrol acetate.
Tablets, capsules or other solid dosage forms.
Every liquid formulation containing megestrol acetate.
A process for micronizing megestrol acetate in the abstract.
A formulation outside the claimed concentration ranges.
A product that does not meet the required suspension characteristic.

The patent's current legal strength is zero as an exclusionary right because the term has expired. The technical disclosure may still be relevant as prior art against later composition patents, but expiration does not prevent a party from practicing the disclosed formulation.

When did U.S. Patent 5,338,732 lose exclusivity?

U.S. Patent 5,338,732 issued on August 16, 1994. Under the pre-Uruguay Round patent term applicable to the application, the ordinary term was generally 17 years from issuance. On that basis, the patent expired on August 16, 2011. [1]

Event	Date
Patent issued	August 16, 1994
Ordinary 17-year expiration	August 16, 2011
Current status	Expired
Current infringement risk	No enforceable patent exclusion based solely on this patent

The patent should not be treated as an active Orange Book barrier today. Any historical patent-term adjustment, patent-term extension or terminal disclaimer should be confirmed in the USPTO patent record and the applicable FDA Orange Book historical listing. The expiration conclusion does not change the commercial analysis: the patent is no longer available to block a new generic launch.

What is the Orange Book status of megestrol acetate oral suspension?

The FDA Orange Book identifies approved drug products and, where applicable, patents and regulatory exclusivity associated with approved products. Megace Oral Suspension was approved as a megestrol acetate oral suspension at 40 mg/mL. Historical Orange Book listings associated with the product included formulation patent information, including U.S. Patent 5,338,732, during the period when the patent remained in force. [2]

Patent listing and patent enforceability are separate questions. A patent may have been listed during the life of an NDA but later expire. An expired Orange Book patent does not support a current Paragraph IV litigation strategy against a generic applicant.

The FDA's current product-specific information should be reviewed by NDA, strength, dosage form and marketing status. The relevant regulatory distinction is between:

Megestrol acetate oral suspension at 40 mg/mL.
Megestrol acetate tablets or other solid products.
Newer or reformulated products, including higher-concentration or altered excipient formulations.
Approved generic products with separate ANDA records.

What Paragraph IV challenges affected the patent?

A Paragraph IV certification asserts that a listed patent is invalid, unenforceable or will not be infringed by the proposed ANDA product. During the patent's active term, a generic applicant seeking approval of a therapeutically equivalent megestrol acetate oral suspension could have faced a Paragraph IV issue if the reference listed patent covered the product.

The statutory framework under the Hatch-Waxman Act creates a potential 30-month stay when the NDA holder or patent owner timely files an infringement action after receiving notice of a Paragraph IV certification. [3]

Because U.S. Patent 5,338,732 expired in 2011, it no longer creates a current 30-month-stay risk. Historical ANDA litigation or certifications may still matter for diligence, but they do not restore the patent's exclusionary term.

No current conclusion about a specific historical Paragraph IV case should be inferred solely from the patent number. FDA listing data, ANDA records, court dockets and settlement documents must be matched to the relevant NDA and generic applicant.

What generic entry risks exist for megestrol acetate suspension?

Current launch risk

The patent itself presents no current generic entry risk. A generic manufacturer can design around the claim limitations or practice the expired disclosure without obtaining a license from the patent owner.

The principal current risks are regulatory and commercial:

Demonstrating pharmaceutical equivalence to the reference product.
Establishing bioequivalence for an oral suspension.
Controlling particle-size distribution and sedimentation.
Maintaining redispersibility through shelf life.
Matching preservative, viscosity, taste and microbiological specifications.
Securing an approved dosage-form and strength pathway.
Competing against existing generic suppliers and authorized products.

Historical launch risk

Before expiration, a 40 mg/mL oral suspension using PEG 1450, polysorbate 80 and a stable flocculated system would have presented a high literal-infringement risk. A design-around could have changed:

The polysorbate type or concentration.
The polyethylene glycol level.
The API concentration.
The flocculation system.
The suspending polymer.
The dosage form or product strength.

A design-around would still need to meet FDA quality and bioequivalence requirements. Avoiding the patent did not guarantee approval.

What formulations are protected by U.S. Patent 5,338,732?

The strongest literal coverage is concentrated around a 40 mg/mL liquid formulation with PEG 1450 at 20% w/v and polysorbate 80 at 0.01% w/v.

Formulation characteristic	Claim exposure
40 mg/mL micronized megestrol acetate	Claims 1-3 and potentially 10
20% w/v polyethylene glycol	Claims 1, 5 and 7
0.01% w/v polysorbate	Claims 1 and 8
Polysorbate 80	Claim 4
Xanthan gum, buffer, sweetener and flavor	Claim 9 and claim 10, depending on exact composition
PEG 1450	Claim 10 expressly
Stable flocculated suspension	Required by claims 1 and 10

Drafting issue in claim 5

Claim 1 requires polyethylene glycol at a concentration "greater than 5%" w/v. Claim 5 recites "from 5% to 30%" w/v. A dependent claim ordinarily narrows its parent claim, so claim 5 is best read as operating within claim 1's greater-than-5% limitation, effectively covering more than 5% through 30%. The literal inclusion of exactly 5% creates an internal inconsistency.

That issue could have affected claim construction during the patent term. It has no practical enforcement consequence now because the patent has expired.

Does the patent cover manufacturing methods or method-of-use claims?

No. The supplied claims are composition claims. They do not expressly claim:

A method of treating anorexia or cachexia.
A method of increasing appetite.
A method of preparing the suspension.
A micronization process.
A packaging system.
A manufacturing control for particle size or flocculation.
A specific dosing regimen.

A manufacturer could have infringed without using the patented manufacturing process if its finished product met the composition claims. Conversely, use of a similar manufacturing process would not alone establish infringement if the resulting product fell outside the claimed composition.

Are biosimilar risks relevant to this patent?

No. Megestrol acetate is a small-molecule active pharmaceutical ingredient, not a biologic. Biosimilar provisions under the Biologics Price Competition and Innovation Act do not apply. [4]

The relevant competitive pathway is the ANDA generic pathway under section 505(j) of the Federal Food, Drug, and Cosmetic Act. Generic applicants address pharmaceutical equivalence and bioequivalence rather than biosimilarity.

Which companies are relevant to the megestrol acetate suspension market?

The principal historical branded product was Megace Oral Suspension, associated with Bristol-Myers Squibb. The product's patent and regulatory history may also involve NDA holders, licensees, authorized distributors and generic manufacturers. Market participation has changed over time as patents expired and generic approvals expanded.

A current competitive review should separate:

The NDA sponsor or current marketing authorization holder.
Generic ANDA applicants and approved manufacturers.
Authorized generic arrangements.
Contract manufacturers.
Products at 40 mg/mL versus other strengths.
Products using different excipient systems.

Patent 5,338,732 does not itself establish ownership of the current product market or identify a continuing license obligation.

How does this patent compare with formulation patents for other oral suspensions?

The patent is typical of drug-product formulation patents in one respect: it protects the combination of active-ingredient particle properties, excipient concentrations and physical performance. Its scope is narrower than a compound patent but can be commercially effective when the formulation is closely aligned with the reference product.

Compared with a method-of-use patent, it places greater emphasis on the product sold by the generic manufacturer. Compared with a manufacturing patent, it allows infringement analysis from the finished dosage form without proving the production steps. Compared with a broad composition patent, it has greater design-around potential because concentration and excipient changes may avoid literal coverage.

Key Takeaways

U.S. Patent 5,338,732 covers micronized megestrol acetate oral suspensions with defined polysorbate and polyethylene glycol ranges.
Claim 10 targets a 40 mg/mL formulation containing PEG 1450, polysorbate 80 and specified excipients.
The claims require a stable flocculated suspension in water.
The patent does not claim megestrol acetate generally, therapeutic use, tablets, or manufacturing methods in general.
The patent issued August 16, 1994, and its ordinary term expired August 16, 2011.
It is not a current enforceable barrier to generic entry.
Paragraph IV issues were relevant only during the patent's active term.
Biosimilar law is not relevant because megestrol acetate is a small molecule.
Current barriers are more likely to involve FDA approval, suspension quality, bioequivalence, manufacturing controls and market competition than this expired patent.

FAQs

Can a generic manufacturer use the exact claim 10 formulation today?

Yes, the patent's expiration removes its patent-based exclusionary right. The manufacturer would still need FDA approval and compliance with applicable quality, manufacturing and bioequivalence requirements.

Does a 40 mg/mL megestrol acetate product automatically infringe claim 3?

No. The product must also contain the required polysorbate and polyethylene glycol concentrations and form a stable flocculated suspension in water.

Does changing PEG 1450 to another polyethylene glycol avoid the patent?

Not necessarily. Claim 10 expressly identifies PEG 1450, but broader claims refer to polyethylene glycol without the same explicit molecular-weight limitation. The full claim language and technical identity of the excipient control the analysis.

Is Megace Oral Suspension still protected by market exclusivity?

U.S. Patent 5,338,732 no longer provides patent exclusivity. Any separate regulatory exclusivity would depend on the specific FDA product record and applicable exclusivity period.

Can a liquid megestrol acetate solution avoid this patent?

A true solution would have a strong argument that it does not satisfy the required suspension limitation. The formulation would still need to comply with FDA requirements for the proposed dosage form and strength.

References

United States Patent and Trademark Office. (1994). U.S. Patent No. 5,338,732, pharmaceutical compositions containing megestrol acetate. U.S. Department of Commerce.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book.
U.S. Food and Drug Administration. (2017). ANDA submissions: Refuse-to-receive standards. U.S. Department of Health and Human Services.
U.S. Food and Drug Administration. (2024). Biosimilar and interchangeable biosimilar products. U.S. Department of Health and Human Services.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	142882	⤷ Start Trial
Australia	1828192	⤷ Start Trial
Australia	647933	⤷ Start Trial
Canada	2071141	⤷ Start Trial
China	1038904	⤷ Start Trial
China	1067580	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,338,732

Summary for Patent: 5,338,732