United States Drug Patent RE32393: Claim Scope, Patent Landscape, Exclusivity, and Generic Risk

United States Patent RE32,393 covers oil-in-water emulsions for intravenous delivery of oil-soluble pharmacologically active agents. Its core limitations are a submicron emulsion, an oil-soluble active agent predominantly dissolved in the oil phase, rapid therapeutic onset, and, for the principal independent composition claims, autoclave stability. The patent also claims specific oils, emulsifiers, glycerol, diazepam formulations, selected active agents, and corresponding intravenous administration methods.

The patent is no longer a live exclusivity barrier. Its commercial importance is historical: it anticipated the use of lipid emulsions to deliver poorly water-soluble drugs and sits within the technical lineage of diazepam emulsions, lipid-based anesthetic products, and later propofol formulations. Reissue status did not restart or extend the underlying patent term. Under 35 U.S.C. §§ 154 and 251, a reissue generally carries the remaining term of the original patent, subject to statutory adjustments and terminal disclaimers.

What technology does U.S. Patent RE32393 protect?

RE32,393 protects a drug-delivery composition rather than a single active pharmaceutical ingredient.

The central invention is an oil-in-water emulsion containing:

A pharmacologically inert lipoid as the hydrophobic phase.
A hydrophilic continuous phase.
An oil-soluble active agent predominantly dissolved in the lipoid.
Lipoid particles with a mean size below one micron.
A rapid onset of an acceptable therapeutic effect.
In the principal intravenous claims, the ability to withstand autoclaving.

The claims are directed to parenteral, and particularly intravenous, delivery. The patent attempts to solve the problem created by oil-soluble drugs that are poorly suited to aqueous injection. Instead of converting the active agent into a water-soluble salt or using a large amount of organic solvent, the claimed formulation dissolves the drug in a physiologically acceptable oil and disperses the oil as fine droplets in water.

Core technical limitations

Limitation	Scope and significance
Oil-in-water emulsion	Requires oil droplets dispersed in an aqueous or hydrophilic phase. A water-in-oil system is outside the literal scope.
Pharmacologically inert lipoid	The oil functions principally as a carrier phase, not as the therapeutic active.
Oil-soluble active agent	The active must be sufficiently lipophilic to be predominantly dissolved in the oil phase.
Mean particle size below 1 micron	A measurable colloidal or submicron limitation. Particle-size testing and sampling methodology would matter in litigation.
Rapid onset	A functional limitation tied to the claimed therapeutic result.
Autoclave stability	Required by claims 1, 21, and 22 and several descendants.
Intravenous administration	Expressly required by claim 21 and the method claims 26 and 41-44.
Selected drug classes or compounds	Narrows the broad composition claims to central depressants, analgesics, muscle relaxants, vasodepressants, or named compounds.

The claims do not require a particular manufacturing process, surfactant concentration, pH, osmolality, droplet-size distribution, container, or infusion device unless those characteristics are incorporated through a dependent claim or are needed to satisfy the stability and particle-size limitations.

How broad is independent claim 1?

Claim 1 is the broadest composition claim in the supplied claim set. It covers an emulsion containing an oil-soluble agent selected from four functional classes:

Central depressants
Analgesics
Muscle relaxants
Vasodepressants

The claim does not limit the composition to diazepam, phenyramidol, soybean oil, egg phosphatide, or any specific stabilizer. Those features appear in dependent claims.

Claim 1 has several potential scope constraints.

The active must be predominantly dissolved in the lipoid

An accused formulation in which the active is principally dissolved in the aqueous phase would not satisfy this limitation. The claim also requires the active to be oil-soluble. A drug suspended as solid particles, encapsulated in a separate nanoparticle, or chemically modified into a water-soluble prodrug may fall outside the literal claim, depending on the formulation structure.

The oil must be dispersed below one micron

The mean-particle-size limitation is central. A formulation with a mean droplet size of one micron or greater would have a strong noninfringement position under the literal claim. The relevant issue would be whether “mean particle size” refers to volume-weighted, number-weighted, intensity-weighted, or another measurement convention. Modern laser-diffraction and dynamic-light-scattering results can produce materially different values.

“Rapid onset” is a functional limitation

Rapid onset creates potential claim-construction and proof issues. The claim does not provide a universal numerical threshold in the supplied text. A patentee would need to establish the relevant comparator, therapeutic endpoint, dose, route, and time period. The limitation may be less predictable than structural requirements such as oil identity or droplet size.

The drug classes are not equally clear

The claim lists “central depressants,” “analgesics,” “muscle relaxants,” and “vasodepressants.” These are functional or pharmacological categories rather than precise chemical genera. Claim 7 expressly identifies phenyramidol as a muscle relaxant, while other claims name individual drugs. Classification disputes could arise for compounds with multiple pharmacological effects.

What do claims 7 and 9-24 add?

The dependent composition claims narrow the broad platform to specific active agents, excipients, oils, and formulations.

Claim group	Principal limitation
Claim 7	Phenyramidol as the active agent
Claims 9 and 14	Soybean, cottonseed, coconut, or olive oil; claim 14 specifically requires soybean oil
Claims 10-12	Stabilizers including phosphatides, polyethylene glycol, polypropylene glycol, polyglycerol monooleate, and polyoxyethylene fatty-acid derivatives
Claim 13	Longer duration than corresponding water-soluble salts
Claims 15 and 18-20	Egg phosphatide, diazepam, acetylated monoglyceride, specified concentrations, soybean oil, and glycerol
Claim 17	Approximately 2.5% glycerol per 100 mL
Claims 21 and 41	Chloralose, benzocaine, or secobarbital with a monoglyceride stabilizer
Claims 22 and 42	Specified analgesics, local anesthetics, barbiturates, or related compounds with a block polymer of ethylene oxide and propylene oxide
Claim 23	Acylated monoglyceride plus a narrower active-agent group
Claim 24	Hexobarbital in the claimed submicron lipoid emulsion
Claim 25	Freezing stability

Claims 18-20 are the most formulation-specific. They describe a diazepam emulsion containing approximately:

0.5 g diazepam per 100 mL
1.2 g phosphatide per 100 mL
5.0 g acetylated monoglyceride per 100 mL
15 g soybean oil per 100 mL
Approximately 2.5 g glycerol per 100 mL

These claims would be narrower and easier to design around than claim 1. A commercial formulation that uses a different oil, stabilizer system, diazepam concentration, or emulsion architecture may avoid literal infringement of the formulation-specific claims while still raising historical relevance under claim 1.

What do the method claims cover?

Claims 26-44 cover intravenous administration of the claimed emulsions. They largely mirror the composition claims but add an affirmative administration step.

A method claim generally requires proof that the accused party performs, directs, or induces intravenous administration of a composition meeting every formulation limitation. For a finished injectable sold with labeling that instructs intravenous use, induced-infringement theories could historically have been relevant. The method claims are not limited to manufacturing the product.

The method claims cover:

Administration of a submicron oil-in-water emulsion.
An oil-soluble active predominantly dissolved in the oil.
Rapid therapeutic onset.
Selected active classes or named compounds.
Selected oils and stabilizers.
Diazepam, phenyramidol, and specified barbiturate or analgesic formulations.
Autoclave or freezing capability where the dependent claim includes those properties.

Because the claims are directed to intravenous administration, an oral, intramuscular, transdermal, or inhaled product would not literally practice the method claims.

What patent landscape surrounds RE32393?

RE32,393 belongs to a broad patent landscape involving lipid emulsions, injectable anesthetics, poorly water-soluble drugs, and parenteral delivery systems.

Historical technology clusters

Technology cluster	Relationship to RE32,393
Diazepam emulsions	Closest historical application; the claims expressly identify diazepam and detailed diazepam formulations.
Intravenous lipid emulsions	Provides the formulation platform and excipient technology.
Propofol emulsions	Later commercial application of a similar oil-in-water delivery concept, but propofol is not among the expressly listed agents in the supplied claims.
Barbiturate emulsions	Claims identify thiopental, pentobarbital, secobarbital, hexobarbital, and related compounds.
Local-anesthetic emulsions	Claims include benzocaine, quatacaine, and lidocaine.
Method-of-use protection	Claims 26-44 cover administration rather than merely the composition.
Manufacturing and sterilization	Autoclave stability is a product-performance limitation, not a standalone manufacturing claim.

The existence of later patents on propofol, lipid emulsions, surfactant systems, particle-size control, container closure, and sterilization does not by itself establish infringement. Each later patent must be compared against the specific claim limitations, including the named active agent, emulsion direction, droplet size, stabilizer, and route of administration.

When did RE32393 lose exclusivity?

The reissue date is not the controlling term date. A reissue patent does not ordinarily receive a new full patent term. The relevant term is tied to the original patent and its filing history under the patent statute applicable at the time.

For an old U.S. patent of this type, the enforceable term would have expired decades ago. The patent therefore presents no current blocking right against generic manufacturers, injectable-drug developers, or competing lipid-emulsion products. Reissue cannot revive an expired original patent or create a new exclusivity period. The applicable statutory framework is 35 U.S.C. §§ 154 and 251.

Exclusivity analysis

Exclusivity category	RE32,393 status
Patent exclusivity	Expired
Reissue exclusivity	No independent new term
FDA new-drug exclusivity	Not created by this patent
Orphan-drug exclusivity	Not apparent from the claim set
Pediatric exclusivity	Not associated with the patent claims
Biosimilar exclusivity	Not applicable; the claims cover small-molecule formulations
Orange Book exclusivity	Patent listing, if historically present, would not create current enforceability after expiration

What is the Orange Book status of RE32393?

The patent itself is not a current regulatory exclusivity right. Orange Book listing is product-specific and depends on whether an approved NDA holder submitted the patent for an approved drug and whether FDA accepted the listing under the applicable rules.

The claimed products include older small molecules such as diazepam, lidocaine, barbiturates, and phenyramidol. A patent covering a formulation or method of use may have been eligible for historical listing if it met the statutory listing criteria. That does not mean every drug named in the claims was listed, nor does it establish that the patent remains listed today.

For current ANDA strategy, the relevant questions are whether a live patent is listed for the specific reference-listed drug, whether a Paragraph IV certification is required, and whether any unexpired formulation or method-of-use patent remains enforceable. RE32,393 itself is not a present exclusivity obstacle.

Were Paragraph IV challenges or settlements relevant?

Paragraph IV challenges are relevant only while a listed patent remains unexpired or otherwise enforceable. Because RE32,393 is expired, a new ANDA applicant would not face a current Paragraph IV risk based on this patent alone.

The supplied material does not establish a specific historical Paragraph IV litigation, settlement, or 30-month stay associated with RE32,393. No reliable conclusion about a particular settlement agreement follows from the claims themselves.

Later disputes involving diazepam emulsions, propofol emulsions, or lipid-based injectable products must be analyzed separately. A later patent may cover:

A different active ingredient.
A particular surfactant combination.
A specified droplet-size distribution.
A sterilization protocol.
A container or dosage form.
A clinical method.
A manufacturing process.

Those later rights are not extensions of RE32,393.

How strong was the patent estate?

The estate was technically broad but legally vulnerable in several areas.

Strengths

Broad platform language covering multiple classes of oil-soluble agents.
Structural limitation to submicron droplets.
Express coverage of intravenous use.
Dependent claims directed to commercially practical oils and stabilizers.
Detailed diazepam formulation claims.
Both composition and method-of-administration claims.

Vulnerabilities

“Rapid onset” is difficult to apply without a precise benchmark.
“Pharmacologically inert” may be disputed for oils with biological effects.
“Predominantly dissolved” requires analytical characterization.
The named drug lists contain spelling and terminology irregularities, including “secobarbitol,” “pentobarbitol,” and “cycloandelate.”
Pharmacological categories such as “central depressants” and “vasodepressants” may raise classification issues.
Submicron measurement depends on the analytical method.
The claims do not broadly cover all lipid nanoparticles, liposomes, self-emulsifying systems, or aqueous solubilizers.

The patent’s practical strength was greatest against a formulation that closely reproduced the disclosed diazepam emulsion: soybean oil, phosphatide, acetylated monoglyceride, glycerol, autoclave stability, and submicron droplets. Its strength was weaker against a product using a different delivery architecture or a chemically modified active.

What generic launch risks exist today?

RE32,393 creates no current generic launch risk because it is expired. Any present risk would come from other rights, such as:

Later formulation patents.
Active-ingredient patents, if any remain.
Use patents.
Manufacturing patents.
Device or container patents.
Regulatory exclusivity.
Trade-secret manufacturing know-how.
Product-quality requirements for injectable emulsions.

For an injectable lipid formulation, the principal non-patent barriers are usually formulation robustness, terminal sterilization, droplet-size control, physical stability, extractables and leachables, endotoxin control, and clinical comparability. Those barriers can delay launch even when the principal formulation patent has expired.

How does RE32393 compare with modern lipid-emulsion patents?

RE32,393 is an early platform patent. Modern patents generally claim narrower technical solutions, including:

Defined droplet-size ranges rather than a single submicron threshold.
Specific phospholipid-to-oil ratios.
Surfactant combinations.
Antioxidants and chelators.
Reduced injection pain.
Improved physical stability.
Freeze-thaw resistance.
Container compatibility.
Particular active agents such as propofol.
Manufacturing parameters and sterilization conditions.

The older patent is broader in drug-class language. Later patents are usually more precise in formulation composition and process control. A current freedom-to-operate analysis must therefore map the complete formulation and process against later patent families rather than rely on RE32,393.

Key Takeaways

RE32,393 covers submicron oil-in-water emulsions for intravenous delivery of oil-soluble drugs.
Claim 1 is the broad platform claim; claims 7 and 9-25 narrow the scope to specific actives, oils, stabilizers, concentrations, and stability properties.
Claims 26-44 cover intravenous administration methods.
The strongest historical embodiment is a diazepam emulsion using soybean oil, phosphatide, acetylated monoglyceride, glycerol, and submicron droplets.
The patent’s central limitations are oil-phase dissolution, mean particle size below one micron, rapid onset, and, in key claims, autoclave stability.
The patent is expired and does not provide current FDA or patent exclusivity.
Paragraph IV, Orange Book, biosimilar, and settlement risks must be assessed against later live patents, not RE32,393.
Modern commercial risk is more likely to arise from later formulation, manufacturing, container, or product-specific patents.

FAQs

Does RE32,393 cover propofol?

Not expressly in the supplied claims. Propofol is an oil-soluble anesthetic that may have technical similarities to the claimed delivery platform, but a propofol product would require a separate claim analysis. The patent is expired in any event.

Does the patent cover all intravenous lipid emulsions?

No. The claims require an oil-soluble active agent predominantly dissolved in the lipoid and a mean lipoid particle size below one micron. Nutritional lipid emulsions without the claimed pharmacologically active agent are outside the literal scope.

Is soybean oil mandatory?

No. Soybean oil is one claimed option. Claim 1 does not require it. Claims 9 and 27 list soybean, cottonseed, coconut, and olive oils, while claim 14 specifically requires soybean oil.

Can a formulation avoid the claims by using a water-soluble salt?

Potentially, if the active is no longer an oil-soluble agent predominantly dissolved in the lipoid. The complete formulation and the chemical identity of the active would determine the result.

Does autoclave stability apply to every claim?

No. Autoclave capability is expressly included in claims 1, 21, and 22 and their relevant method counterparts. It is not necessarily an independent limitation of every dependent or method claim in the supplied set.

References

United States Patent and Trademark Office. (n.d.). U.S. Patent No. RE32,393, reissue patent claims supplied by requester. U.S. Department of Commerce.
United States Code. (2023). 35 U.S.C. § 154: Contents and term of patent; provisional rights. Office of the Law Revision Counsel.
United States Code. (2023). 35 U.S.C. § 251: Reissue of defective patents. Office of the Law Revision Counsel.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. U.S. Department of Health and Human Services.
U.S. Food and Drug Administration. (2024). Orange Book: Approved drug products with therapeutic equivalence evaluations, patent and exclusivity information. U.S. Department of Health and Human Services.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Sweden	12159/67	Sep 1, 1967

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Germany	1792410	⤷ Start Trial
Denmark	129272	⤷ Start Trial
France	1593013	⤷ Start Trial
France	8152	⤷ Start Trial
United Kingdom	1229967	⤷ Start Trial
Netherlands	6812429	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: RE32393

Summary for Patent: RE32393