US Patent 5,931,809: Claim Scope, Expiration, DepoDur Protection, and Patent Landscape

US Patent 5,931,809 covers methods of administering therapeutic compounds, particularly opioids, into the epidural space using sustained-release multivesicular liposomes. Its broadest claim requires the combination of four elements: a therapeutic compound, encapsulation in a multivesicular liposome formulation, phospholipid content below 10% by weight per volume, and epidural administration.

The patent is no longer an enforceable barrier to U.S. market entry because its statutory patent term expired in 2016. Its historical importance was tied to DepoDur, an extended-release epidural morphine product based on the DepoFoam multivesicular liposome platform. The patent does not broadly cover epidural morphine, ordinary liposomal formulations, or every sustained-release epidural product.

What does US Patent 5,931,809 cover?

US 5,931,809 covers therapeutic methods rather than a standalone drug composition. Independent claim 1 is directed to:

A method of epidural administration;
To a vertebrate;
Of a therapeutic compound;
Encapsulated in a multivesicular liposome formulation;
Containing less than 10 weight percent by volume of phospholipid;
Having a sustained release rate; and
Introducing the formulation epidurally.

The patent therefore requires simultaneous satisfaction of formulation and administration limitations. A product must not merely contain morphine or use a liposome. The relevant formulation must be a multivesicular liposome with the specified phospholipid threshold and sustained-release characteristics, and it must be administered epidurally.

The patent’s claims are summarized below.

Claim group	Subject matter	Key limitation
1-3	General epidural administration	Vertebrate, mammal, human
4-8	Opioids and opioid antagonists	Morphine sulfate, hydromorphone, naloxone, naltrexone
9-10	Neurotrophic and neuroactive compounds	Growth factors, dopamine, catecholamines, GABA, neostigmine
11-12	Epidural catheter delivery	Catheter, including downward cervical insertion
13-14	Administration format	Single dose and dispersion system
15	Peptides and peptidomimetics	Broad therapeutic class
16-17	Specific opioids and endogenous peptides	Morphine-related compounds, fentanyl compounds, enkephalins and endorphins
18	Needle delivery	Hypodermic needle inserted into epidural space
19-23	Respiratory-depression method	One-dose epidural analgesic formulation, including morphine at 1-60 mg

When did US Patent 5,931,809 expire?

US Patent 5,931,809 expired in 2016 under the applicable U.S. patent-term rules. The patent was granted on August 3, 1999. Its term was governed by the 20-year term measured from the applicable nonprovisional filing or priority framework rather than the former 17-year term from grant.

The expiration removes the patent as a current U.S. exclusion right. It does not eliminate its value as prior art against later patent applications. The patent can still affect validity analysis for later claims directed to epidural multivesicular liposomes, sustained-release epidural opioids, or related DepoFoam formulations.

Event	Date or period
U.S. patent grant	August 3, 1999
Historical product relevance	DepoDur epidural morphine
Expected statutory expiration	2016
Current enforceability	Expired
Current Paragraph IV relevance	None for this expired patent

Any patent-term adjustment, terminal disclaimer, or related continuation must be evaluated from the official USPTO Patent Center record. The expiration of 5,931,809 does not establish expiration of every patent directed to the DepoFoam platform.

How broad is claim 1 of US 5,931,809?

Claim 1 is technically broad but structurally constrained. It does not limit the therapeutic compound to morphine or opioids. The compound can be a small molecule, peptide, peptidomimetic, neuroactive agent, opioid antagonist, or another therapeutic compound, provided the formulation and administration limitations are met.

The most important limitations are:

Multivesicular liposome requirement

A multivesicular liposome is not synonymous with a conventional unilamellar liposome, multilamellar liposome, lipid nanoparticle, micelle, or polymeric microparticle. Multivesicular liposomes contain multiple internal aqueous chambers within a lipid-based particle. The structural distinction is important in infringement and validity analysis.

A sustained-release liposomal formulation that lacks the multivesicular architecture may fall outside claim 1 even if it produces a similar release profile.

Less than 10 weight percent by volume of phospholipid

The claim includes a quantitative phospholipid limitation. The wording combines weight and volume concepts, creating potential issues regarding:

The precise denominator used for volume;
Whether the measurement applies to the final formulation or a component phase;
The meaning of "phospholipid" when several lipid species are used;
Whether the threshold is measured before or after drug loading;
Analytical reproducibility across batches.

This limitation can create a non-infringement position where a competing formulation uses a higher lipid concentration, a different lipid system, or a non-liposome sustained-release carrier. It can also create an enablement, written-description, or indefiniteness issue if the specification does not provide a reliable method for applying the threshold across the full claim scope.

Sustained release

The claim does not specify a fixed duration, release percentage, pharmacokinetic profile, or in vitro test method. The term therefore depends heavily on the patent specification, prosecution history, and the product’s demonstrated release behavior.

A formulation that produces prolonged epidural exposure may satisfy the limitation even if the release profile differs from DepoDur. Conversely, a formulation with delayed onset but no meaningful sustained-release behavior may not satisfy it.

Epidural administration

The claim requires administration into the epidural space. Intrathecal, intravenous, subcutaneous, intramuscular, and local infiltration administration do not satisfy this limitation. Administration through a catheter or needle is not required by claim 1, but claims 11, 12, and 18 expressly narrow the delivery route to those devices.

What formulations are protected by the patent?

The patent protects methods using multivesicular liposome dispersions with sustained release. It does not claim every composition detail needed to manufacture such particles.

The claims cover formulations containing:

Morphine sulfate;
Hydromorphone;
Codeine;
Hydrocodone;
Levorphanol;
Oxycodone;
Oxymorphone;
Diacetyl morphine;
Buprenorphine;
Nalbuphine;
Butorphanol;
Pentazocine;
Methadone;
Fentanyl;
Sufentanil;
Alfentanil;
Naloxone;
Naltrexone;
Enkephalins;
Endorphins;
Casomorphin;
Kyotorphin;
Bioactive fragments;
Peptides and peptidomimetics; and
Various neurotrophic or neuroactive compounds.

Claims 4-6 and 16-17 are particularly relevant to opioid products. Claim 5 is limited to morphine sulfate. Claim 22 narrows the morphine method to a dose of approximately 1 mg to 60 mg.

The patent has no independent composition claim. A formulation manufacturer would therefore face infringement exposure primarily when the formulation is used in the claimed epidural method, not merely because the formulation is made or sold.

Does the patent cover DepoDur?

Yes, the claim structure is closely aligned with DepoDur, an extended-release epidural morphine product based on a multivesicular liposome delivery system. DepoDur contained morphine sulfate in the DepoFoam platform and was administered into the epidural space for postoperative pain management.

The most relevant patent claims for DepoDur were claims 1, 4, 5, 13, 14, 19, 21, and 22. Claim 21 identifies morphine sulfate, while claim 22 covers a morphine dose of about 1 mg to 60 mg.

FDA approved DepoDur under NDA 021281 in 2004. The product was subject to opioid safety restrictions, including monitoring for delayed respiratory depression. The FDA approval concerned the specific drug product and its clinical use; it did not convert every epidural morphine formulation into a covered product.

What does claim 19 cover?

Claim 19 covers a method for ameliorating respiratory depression in a patient administered an analgesic compound. The method requires:

Epidural administration;
One and only one dose;
An analgesic compound;
Encapsulation in a multivesicular liposome formulation; and
Phospholipid content below 10% by weight per volume.

Claims 20-23 narrow the method to opioids and specified dose ranges, including morphine sulfate at approximately 1 mg to 60 mg.

Claim 19 presents a claim-construction issue because the claimed administered compound is an analgesic, while opioid analgesics are also known to cause respiratory depression. The phrase "ameliorating respiratory depression" must be read with the specification and prosecution history. Potential interpretations include reduced respiratory-depression risk resulting from sustained release, management of analgesia with reduced peak exposure, or treatment of a patient in whom respiratory depression is a clinical concern.

The claim does not expressly recite naloxone or another reversal agent in the independent claim. Claims 20-23 focus on analgesic opioids, including morphine and hydromorphone.

How strong is the patent estate for multivesicular epidural opioids?

The patent’s historical estate was technically significant but commercially narrower than a composition patent. Its strength came from the combination of:

A specialized multivesicular liposome platform;
Sustained epidural delivery;
Opioid payloads;
Single-dose administration; and
A defined low-phospholipid formulation range.

Its principal weaknesses were claim-specific. The patent did not prevent development of:

Non-liposomal sustained-release formulations;
Unilamellar or multilamellar liposomes;
Polymer-based depot systems;
Intrathecal or non-epidural delivery;
Immediate-release epidural morphine;
Formulations outside the phospholipid threshold; or
Products using a different route and dosage form.

Because the patent expired, these distinctions now matter primarily for historical freedom-to-operate analysis, prior-art review, and evaluation of later patents.

What is the Orange Book status of DepoDur and this patent?

The relevant regulatory product was DepoDur, not US 5,931,809 itself. Patent listing in the FDA Orange Book depends on whether the patent was submitted for the approved NDA, met the statutory listing requirements, and remained listed during the product’s commercial life.

A method-of-use patent can be listed in the Orange Book when it claims an approved method of using the drug. An expired patent does not create a current stay or enforceable exclusivity period. Any historical Orange Book listing for DepoDur would have had no continuing blocking effect after the patent expired.

The Orange Book should be distinguished from the FDA Purple Book. The Purple Book concerns licensed biological products and biosimilars. DepoDur is a drug product, not a biologic, so biosimilar procedures do not apply.

Were there Paragraph IV challenges or generic litigation?

A Paragraph IV certification is relevant only while a listed patent remains within the Orange Book framework and has not expired. For US 5,931,809, the patent’s 2016 expiration means that it cannot support a current Paragraph IV litigation strategy.

No current generic challenge can be directed at this expired patent. A historical Abbreviated New Drug Application or NDA dispute involving DepoDur would need to be analyzed against the complete Orange Book history, FDA approval records, and federal court docket. The supplied claim text does not establish a particular Paragraph IV filing, settlement agreement, or final judgment.

The principal commercial issue today is therefore not litigation risk under 5,931,809. It is whether later, unexpired patents cover the specific multivesicular liposome composition, manufacturing process, formulation excipients, device, dosage regimen, or approved use.

What manufacturing and intellectual-property barriers remain?

Expiration of 5,931,809 does not eliminate technical barriers associated with multivesicular liposomes. A competing manufacturer may still need to address:

Reproducible particle formation;
Encapsulation efficiency;
Internal aqueous chamber structure;
Particle-size distribution;
Sterility and endotoxin control;
Drug loading consistency;
Burst-release control;
Stability during storage;
Syringe and catheter compatibility;
Epidural safety;
Scale-up of the manufacturing process; and
Later patents covering lipid combinations or process conditions.

Manufacturing patents can remain commercially relevant even after a use patent expires. A company that avoids the expired method claims may still infringe an unexpired process or formulation patent owned by the original developer or a later licensee.

How does US 5,931,809 compare with ordinary epidural morphine products?

Product or approach	Multivesicular liposome required?	Sustained release required?	Epidural route required?	Exposure to claim 1
Conventional epidural morphine solution	No	No	Yes	Low
Conventional extended-release polymer depot	No	Yes	Yes	Low
Unilamellar liposomal morphine	No, unless construed otherwise	Possibly	Yes	Fact dependent
Multivesicular liposomal morphine	Yes	Yes	Yes	Historically high
Intrathecal multivesicular liposome	Yes	Yes	No	Low under claim 1
Multivesicular liposomal hydromorphone	Yes	Yes	Yes	Historically high
Intravenous multivesicular liposome	Yes	Yes	No	Outside claim 1

This comparison reflects claim elements, not current enforceability. The patent expired in 2016.

What generic entry risks exist?

US 5,931,809 no longer creates a generic-entry block. A generic or follow-on product can enter without obtaining a license to this expired patent, subject to FDA approval and compliance with other unexpired rights.

The commercial entry risks are more likely to involve:

FDA requirements for an equivalent dosage form and route;
Clinical or pharmacokinetic bridging for extended epidural exposure;
Controlled-substance manufacturing and distribution requirements;
Sterility and injectable-product controls;
Device compatibility;
Later formulation or process patents; and
Product-liability exposure associated with delayed respiratory depression.

An ordinary generic morphine injection would not automatically be a substitute for an extended-release multivesicular product. The relevant regulatory pathway may depend on whether the proposed product is pharmaceutically equivalent, therapeutically equivalent, or a new drug requiring an NDA.

What is the competitive landscape?

The commercial field has included:

DepoDur and related DepoFoam products;
Conventional epidural morphine injections;
Extended-release epidural or intrathecal delivery systems;
Polymer-based implantable or injectable depots;
Patient-controlled epidural analgesia;
Intrathecal opioid products; and
Non-opioid regional analgesic systems.

The key competitive distinction is duration of analgesia and monitoring burden. A single-dose sustained-release epidural formulation can reduce repeat dosing but raises concerns about delayed respiratory depression, catheter placement, neurological monitoring, and rescue treatment.

Patent ownership and licensing in this field have historically centered on the DepoFoam platform and its successors. The supplied information does not establish a specific licensing agreement, assignment chain, or current owner beyond the patent record itself. The patent’s expired status means that any present licensing value would arise from separate unexpired patents, know-how, manufacturing rights, trademarks, or regulatory assets.

Key Takeaways

US 5,931,809 claims methods of epidurally administering sustained-release multivesicular liposome formulations.
Claim 1 requires a therapeutic compound, multivesicular liposome encapsulation, less than 10% phospholipid by weight per volume, sustained release, and epidural administration.
Claims 4-6 and 16-17 cover opioid embodiments, including morphine sulfate and hydromorphone.
Claims 19-23 address single-dose epidural analgesic administration and include morphine doses of approximately 1 mg to 60 mg.
The patent is a method patent, not a broad composition patent.
It was historically relevant to DepoDur and the DepoFoam delivery platform.
The U.S. patent expired in 2016 and does not create current enforceable exclusivity.
It does not block ordinary epidural morphine, non-multivesicular liposomes, polymer depots, or non-epidural delivery.
Current freedom-to-operate analysis must focus on later patents covering formulation composition, manufacturing, devices, dosage regimens, and approved uses.
FDA Orange Book and Paragraph IV issues are historical for this patent; the expired patent cannot support a current U.S. patent-exclusion strategy.
Biosimilar procedures do not apply because DepoDur is a drug product rather than a biologic.

FAQs

Does US 5,931,809 claim morphine itself?

No. It claims a method of using morphine sulfate, among other compounds, when morphine is encapsulated in a sustained-release multivesicular liposome formulation and administered epidurally.

Does the patent cover intrathecal DepoFoam morphine?

Claim 1 requires epidural administration. Intrathecal administration is outside the literal scope of that claim, although separate patents may cover intrathecal formulations or uses.

Is a conventional epidural morphine injection covered?

Generally no, because the claims require encapsulation in a multivesicular liposome formulation with sustained release and the specified phospholipid limitation.

Can a company obtain a license to the expired patent?

A license is not required to practice an expired U.S. patent. Commercial parties may still negotiate licenses for separate unexpired patents, manufacturing know-how, trademarks, regulatory assets, or technology rights.

Does patent expiration mean DepoDur can be marketed without FDA approval?

No. Patent expiration removes the patent barrier but does not eliminate FDA approval, controlled-substance, sterile injectable, labeling, manufacturing, or clinical requirements.

References

United States Patent and Trademark Office. (1999). Epidural administration of multivesicular liposomes, U.S. Patent No. 5,931,809. https://patents.google.com/patent/US5931809
U.S. Food and Drug Administration. (2004). DepoDur: Morphine sulfate extended-release liposome injection, prescribing information. NDA 021281. https://www.accessdata.fda.gov
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations, Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/orange-book
U.S. Patent and Trademark Office. (n.d.). Patent Center. https://patentcenter.uspto.gov
U.S. Food and Drug Administration. (n.d.). Purple Book: Database of licensed biological products. https://purplebooksearch.fda.gov

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	6491196	⤷ Start Trial
Australia	699177	⤷ Start Trial
Brazil	9609717	⤷ Start Trial
Canada	2226870	⤷ Start Trial
China	1085944	⤷ Start Trial
China	1195286	⤷ Start Trial
European Patent Office	0839027	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,931,809

Summary for Patent: 5,931,809