US Patent 5,932,547 covers stable nonaqueous peptide formulations using polar aprotic solvents, with claim branches directed to LHRH compounds, leuprolide, glucagon, GLP-1, and GLP-2. The patent issued on August 3, 1999, and its enforceable term expired in 2017. It therefore presents historical freedom-to-operate relevance but no current US blocking right.

US Drug Patent 5,932,547: Scope, Claims, Expiration, and Patent Landscape

What does US Patent 5,932,547 cover?

US Patent 5,932,547, titled “Stable Non-Aqueous Formulations of Peptides,” claims pharmaceutical formulations containing a peptide and a polar aprotic solvent.[1]

The central technical proposition is that a concentrated peptide can remain stable in a nonaqueous solvent, including a solvent that reduces or prevents gel formation. The claims also address formulations intended for implantable drug-delivery systems and formulations that remain stable under elevated temperature or irradiation.

The patent has three principal claim families:

Claim family	Core subject matter	Representative claims
LHRH-related formulations	LHRH peptides in a polar aprotic solvent	Claims 1-14
Mixed-solvent formulations	Peptide, polar aprotic solvent, and nonaqueous protic solvent	Claims 9, 16-25
Glucagon-family formulations	Glucagon, GLP-1, or GLP-2 in a polar aprotic solvent	Claims 15, 26-34

The most commercially important disclosed embodiment is a concentrated leuprolide formulation in DMSO, including approximately 30% to 50% leuprolide acetate and a formulation containing 370 mg of leuprolide in 1 mL of DMSO.

What are the independent claims in US 5,932,547?

The independent claims are claims 1, 9, and 15.

Claim 1: LHRH-related peptide plus polar aprotic solvent

Claim 1 requires:

A stable nonaqueous formulation;
At least one peptide compound;
At least one polar aprotic solvent; and
The peptide must be an LHRH-related compound.

The claim is composition-focused. It does not require an implant, a particular delivery route, a particular concentration, or DMSO specifically.

The phrase “stable” is modified by the specification and dependent claims, but claim 1 itself does not expressly require a defined storage period or temperature. A formulation that satisfies the claim would need to meet the patent’s technical meaning of stability and contain the required peptide-solvent combination.

Claim 9: Peptide, polar aprotic solvent, and nonaqueous protic solvent

Claim 9 adds a nonaqueous protic solvent to the formulation. Its required elements are:

A peptide compound;
A polar aprotic solvent; and
A nonaqueous protic solvent.

Claim 9 is broader in peptide identity than claim 1 because it does not initially limit the peptide to an LHRH-related compound. Claim 25 later narrows the claim to an LHRH-related peptide.

Claim 15: Glucagon, GLP-1, or GLP-2

Claim 15 covers a stable nonaqueous formulation comprising:

A peptide compound;
A polar aprotic solvent; and
A peptide selected from glucagon, glucagon-like peptide-1, or glucagon-like peptide-2.

The claim predates the commercial development of many modern GLP-1 products. Its wording reaches a broad formulation class, but enforceability ended with patent expiration.

How broad are the solvent claims?

The broadest solvent language is “at least one polar aprotic solvent.” Claims 10 and 22 identify DMSO and DMF as narrower examples, but those claims do not limit claims 1, 9, or 15 to only those solvents.

Potentially relevant polar aprotic solvents include:

Dimethyl sulfoxide, or DMSO;
Dimethylformamide, or DMF;
N-methyl-2-pyrrolidone, or NMP;
Dimethylacetamide, or DMAc; and
Other solvents with comparable polarity and lack of an acidic hydrogen.

The claim does not require the solvent to be used as the only liquid vehicle. A formulation containing a polar aprotic solvent together with another excipient or solvent could fall within the literal scope if the remaining limitations are met.

The specification’s disclosure of “anti-gellant” behavior is important. Claims 11 and 23 expressly recite that the polar aprotic solvent provides an anti-gellant effect. Those claims require more than the mere presence of a solvent; the solvent must perform the claimed functional role.

What formulations are protected by claims 12 and 13?

Claims 12 and 13 are the most formulation-specific claims.

Claim	Required formulation
12	Approximately 30% to approximately 50% by weight leuprolide acetate in DMSO
13	370 mg leuprolide in 1 mL DMSO

Claim 12 uses “consists essentially of,” which generally excludes ingredients that materially change the basic and novel characteristics of the formulation while allowing components that do not materially affect those characteristics.

Claim 13 is narrower because it specifies the peptide-to-solvent proportion. A formulation containing materially different concentrations, a different leuprolide salt, or a different solvent would face a stronger noninfringement position under the literal wording of the claim. Doctrine-of-equivalents analysis would be separate and would have been relevant only during the enforceable patent term.

What peptide drugs fall within the claim structure?

The claims identify the following peptide categories:

Peptide or class	Relevant claims	Commercial relevance
Leuprolide	4, 12, 13, 25	Prostate cancer, endometriosis, uterine fibroids, central precocious puberty
LHRH	4, 25	Hormonal regulation
Nafarelin	4	GnRH agonist
Goserelin	4	Hormone-sensitive cancers and reproductive indications
Glucagon	15	Hypoglycemia treatment
GLP-1	15	Metabolic and endocrine applications
GLP-2	15	Intestinal rehabilitation and related indications

Claim 4 is a closed Markush limitation because it states that the peptide is selected from leuprolide, LHRH, nafarelin, and goserelin. A different LHRH analog may fall under claim 1 but outside claim 4.

Claims 15 and 26-34 use a separate peptide class. They do not require leuprolide or an LHRH analog.

What stability requirements do the dependent claims impose?

The patent includes three temperature-and-time stability limitations:

Claims	Stability requirement
5, 18, 28	Stable at 80°C for at least two months
6, 19, 29	Stable at 37°C for at least three months
7, 20, 30	Stable at 37°C for at least one year

These limitations narrow the independent claims. A formulation that satisfies claim 1 but lacks the specified one-year stability would not satisfy claim 7 unless it met that limitation in practice.

Claims 14, 24, and 34 add stability after irradiation. Claims 8, 21, and 31 require that the formulation be adapted for use in an implantable drug-delivery device.

The stability claims are technically significant because peptide degradation, aggregation, gelation, and solvent compatibility can vary with:

Peptide concentration;
Counterion or salt form;
Water content;
Container composition;
Temperature;
Radiation dose;
Residence time; and
Delivery-device materials.

Does the patent cover Eligard or other leuprolide products?

Eligard is a leuprolide acetate product using the ATRIGEL delivery system. The product uses a polymeric delivery vehicle and NMP-based formulation technology. NMP is a polar aprotic solvent.

At a high level, an NMP-containing leuprolide formulation could satisfy the broad structural elements of claim 1 if it is a stable nonaqueous formulation containing leuprolide and NMP. It would not satisfy claim 12, which is limited to leuprolide acetate in DMSO, or claim 13, which specifies 370 mg leuprolide per 1 mL DMSO.

The patent’s expiration removes current infringement exposure for US commercial products. The comparison remains relevant for historical patent mapping and for identifying the technical overlap between nonaqueous peptide formulations and in situ depot systems.

Product or technology	Peptide	Principal formulation concept	Relationship to US 5,932,547
Lupron Depot	Leuprolide acetate	Depot microspheres and injectable suspension	Broad peptide-formulation overlap is limited by product architecture
Eligard	Leuprolide acetate	Polymer depot formed from an NMP-containing system	Potential historical overlap with broad polar-aprotic-solvent language
Fensolvi	Leuprolide acetate	Subcutaneous depot formulation	Requires product-specific formulation and patent review
DMSO leuprolide concept	Leuprolide	Concentrated DMSO solution	Directly aligned with claims 12 and 13

When did US Patent 5,932,547 lose exclusivity?

US Patent 5,932,547 expired in 2017 under the 20-year patent-term framework applicable to the application. The patent issued on August 3, 1999, but the issue date did not determine the end of the term under the modern patent-term statute.[1][2]

Event	Date or period
Patent issued	August 3, 1999
Statutory patent term	20 years from the applicable nonprovisional filing date
Enforceable US term ended	2017
Current status	Expired
Current blocking effect	None for new US activities

The patent may remain visible in historical patent databases and may have appeared in prior diligence reports, but an expired patent cannot support a new US infringement action for activities occurring after expiration.

What is the Orange Book status of US 5,932,547?

US Patent 5,932,547 is not a current Orange Book exclusivity barrier. The FDA Orange Book identifies patents and regulatory exclusivities associated with approved drug products, but an expired patent does not provide current market exclusivity.[3]

The patent should not be treated as equivalent to:

A current listed formulation patent;
A current method-of-use patent;
New chemical entity exclusivity;
Pediatric exclusivity; or
A patent term extension.

For leuprolide products, current freedom-to-operate analysis would focus on later patents covering depot systems, polymer compositions, administration schedules, dosage forms, manufacturing processes, and specific indications.

Are there Paragraph IV challenges involving this patent?

A Paragraph IV certification is an ANDA applicant’s position that a listed patent is invalid, unenforceable, or will not be infringed. The claim set for US 5,932,547 does not itself establish that an ANDA applicant filed a Paragraph IV challenge.

Because the patent expired in 2017, a present-day generic applicant would not need to rely on a Paragraph IV certification to launch against this patent. The relevant question would be whether later, unexpired patents are listed for the reference product.

Historical Paragraph IV activity involving leuprolide products may have targeted other patents, including patents covering depot polymers, dosing regimens, syringe systems, or product-specific compositions. Those patents should be analyzed separately from US 5,932,547.

What is the patent landscape around nonaqueous peptide formulations?

The relevant patent landscape has five layers.

1. Peptide stabilization

These patents claim excipients, solvents, buffers, surfactants, antioxidants, salts, and water-activity controls that reduce peptide degradation or aggregation.

2. In situ forming depots

These patents claim biodegradable polymers dissolved in NMP or related solvents. After injection, the solvent exchanges with water and the polymer forms a depot.

3. Implantable delivery devices

These patents claim reservoirs, osmotic pumps, injectable implants, drug-loaded matrices, and controlled-release systems. Claim 8 of US 5,932,547 connects its formulation claims to this device category.

4. Drug-specific formulations

Later patents may claim leuprolide acetate particle size, polymer molecular weight, release kinetics, concentration, reconstitution systems, or administration intervals.

5. Manufacturing and sterilization

Claims involving irradiation, aseptic processing, container closure systems, peptide loading, solvent drying, and stability testing can create practical barriers even when the core composition patent has expired.

How strong was the patent estate?

The patent had meaningful historical breadth because the independent claims combined:

A broad peptide category;
A broad polar aprotic-solvent category;
Stability language;
Implantable-device applications; and
Separate branches for LHRH and glucagon-family peptides.

Its strongest claims were likely claims 12 and 13 because they identified a specific leuprolide-DMSO composition. Its broadest claims were claims 1, 9, and 15, but broad claims are more exposed to prior-art and claim-construction challenges.

The estate’s present strength is zero as an enforceable US right because the patent expired. Its remaining value is technical and historical:

It identifies an early nonaqueous peptide formulation approach;
It may be relevant to prosecution-history estoppel or prior-art analysis;
It can inform freedom-to-operate searches for later patents; and
It may affect validity analysis of later continuation or improvement patents if its disclosure predates them.

What generic launch risks exist today?

US 5,932,547 creates no current generic launch risk. A generic or follow-on manufacturer can develop a DMSO, NMP, DMF, or other polar-aprotic-solvent peptide formulation without infringing this expired patent.

Current risk would arise from later rights covering:

A specific leuprolide formulation;
A polymeric depot;
A drug-device combination;
A delivery interval;
A method of treating a particular indication;
A manufacturing process;
A container or prefilled delivery system; or
A formulation parameter not disclosed in the expired patent.

For GLP-1 products, the major current patent risks generally involve molecule-specific, formulation-specific, device, and method-of-use patents rather than this expired broad solvent patent. GLP-1 products may enter through different regulatory pathways depending on the active ingredient, reference product, dosage form, and FDA classification.[4]

Key Takeaways

US Patent 5,932,547 claims stable nonaqueous peptide formulations containing a polar aprotic solvent.
Claims 1-14 focus primarily on LHRH-related peptides, including leuprolide.
Claims 12 and 13 specifically target leuprolide-DMSO formulations, including 370 mg leuprolide per 1 mL DMSO.
Claims 15 and 26-34 cover glucagon, GLP-1, and GLP-2 formulations.
Claims 8, 21, and 31 extend the formulation concepts to implantable drug-delivery systems.
The patent issued August 3, 1999, and expired in 2017.
It is not a current US Orange Book exclusivity barrier.
No current Paragraph IV risk arises from this expired patent.
Historical overlap is most relevant to nonaqueous leuprolide depot systems, including NMP-based delivery technologies.
Current freedom-to-operate work should focus on later formulation, device, manufacturing, dosage-regimen, and method-of-use patents.

FAQs About US Patent 5,932,547

Does US Patent 5,932,547 cover NMP?

Potentially under its broad polar aprotic-solvent claims, if the other elements are met. It does not cover NMP under the narrower claims that expressly require DMSO or DMF.

Does the patent cover semaglutide or tirzepatide?

The patent’s claim language identifies glucagon, GLP-1, and GLP-2, but it does not expressly name semaglutide or tirzepatide. Any historical analysis would require claim construction and comparison of the peptides. The patent is expired in any event.

Can a company commercialize a leuprolide-DMSO formulation today?

US Patent 5,932,547 does not prevent commercialization because it expired in 2017. Later patents, regulatory requirements, formulation performance, and product-specific rights remain separate issues.

Is US 5,932,547 a formulation patent or a method-of-use patent?

It is primarily a composition and formulation patent. The claims do not principally recite treating a disease or administering a peptide to a patient.

Does patent expiration eliminate FDA approval requirements?

No. Patent expiration removes the patent barrier but does not remove requirements for FDA approval, quality manufacturing, stability data, safety testing, bioequivalence, or applicable drug-delivery-device controls.

References

United States Patent and Trademark Office. (1999). U.S. Patent No. 5,932,547, Stable non-aqueous formulations of peptides.
35 U.S.C. § 154. Patent term and right to exclude.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
U.S. Food and Drug Administration. (2024). Purple Book: Database of licensed biological products.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	007714	⤷ Start Trial
Austria	224199	⤷ Start Trial
Austria	263570	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,932,547

Summary for Patent: 5,932,547