United States Drug Patent 5,114,948: Scope, Claims, Expiration, and Patent Landscape for Pergolide Mesylate

U.S. Patent No. 5,114,948 protected oxidation-stabilized pharmaceutical compositions containing pergolide or a pergolide salt, particularly pergolide mesylate stabilized with L-methionine. The patent also covered selected light-stabilizing agents, including polyvinylpyrrolidone, propyl gallate, and alpha-tocopherol. The patent issued on May 19, 1992, and its 17-year pre-URAA term expired on May 19, 2009, absent an earlier terminal disclaimer or other limiting event.[1]

The patent is therefore no longer an enforceable barrier to U.S. generic manufacture, formulation, sale, or use. Its commercial relevance is historical: it likely supported the stability profile of pergolide mesylate tablets, including the Permax product, but it cannot presently block a competing product.

What does U.S. Patent 5,114,948 protect?

The patent protects a formulation solution to pergolide instability. Its claims target two degradation pathways:

Oxidative decomposition of pergolide or a pergolide salt.
Light-induced decomposition, when a separate light-stabilizing compound is included.

The core inventive concept is the incorporation of an amino-acid stabilizer, principally L-methionine, into a pergolide pharmaceutical composition.

Claim group	Subject matter	Principal limitation
Claims 1-6	Oxidation-stabilized compositions	Methionine, cysteine, or cysteine hydrochloride
Claims 7-12	Oxidation- and light-stabilized compositions	Oxidation stabilizer plus selected light stabilizer
Claims 13-17	Stabilization method claims	Incorporating the oxidation stabilizer into the composition

The claims are formulation claims, not claims to pergolide as a chemical entity. They do not broadly cover pergolide, pergolide mesylate, dopamine agonist activity, or treatment of Parkinson's disease.

What is the claim scope of the independent claims?

Claim 1: oxidation-stabilized pergolide composition

Claim 1 requires all of the following:

Pergolide or a salt thereof;
A therapeutically effective amount;
Methionine, cysteine, or cysteine hydrochloride;
An amount of the selected stabilizer sufficient to stabilize against oxidation; and
Pharmaceutically acceptable excipients.

The claim is open-ended because it uses "comprising." A product can fall within the claim even if it contains additional active ingredients, excipients, coatings, preservatives, or stabilizers.

The claim does not require pergolide mesylate. A composition containing another pergolide salt could satisfy claim 1 if the other limitations are met. It also does not specify a dosage form. Tablets, capsules, powders, granules, or other pharmaceutical presentations could potentially fall within the claim.

The functional language "in an amount sufficient to effect stabilization to oxidation" creates an evidentiary issue. In an infringement dispute, the patentee would need to establish that the stabilizer performs the claimed stabilizing function in the accused composition. The presence of methionine alone would not necessarily resolve every technical question, particularly where the product contains other antioxidants or where stability data show no meaningful oxidation benefit.

Claim 13: method of stabilizing a pergolide composition

Claim 13 covers a method comprising incorporating the specified stabilizer into a pergolide composition. It requires:

Pergolide or a pergolide salt;
A therapeutically effective amount;
Pharmaceutically acceptable excipients; and
Incorporation of methionine, cysteine, or cysteine hydrochloride in an amount sufficient to stabilize against oxidation.

The method claims are narrower in practical operation than a composition claim because they focus on the act of incorporating the stabilizer. They could have been relevant to manufacturing processes or formulation development, but they expired with the patent.

How narrow are claims 2 through 6?

Claims 2 through 6 progressively narrow claim 1.

Claim	Additional limitation
2	Pergolide is pergolide mesylate
3	Stabilizer is L-methionine
4	L-methionine is 0.1% to 2.0% by total weight
5	L-methionine is 0.2% to 1.0% by total weight
6	Approximately 300 mg tablet with approximately 73 mcg pergolide mesylate and approximately 1 mg L-methionine

Claim 6 is the most product-specific claim in this group. Its disclosed formulation corresponds to approximately:

0.0243% pergolide mesylate by weight;
0.333% L-methionine by weight; and
Approximately 299 mg of other excipients.

The "approximately" language provides some practical tolerance, but it does not eliminate the need to evaluate the accused product's actual composition and tablet weight. Claims 4 and 5 establish broader numerical ranges around L-methionine. Claim 6 narrows the formulation to a low-dose tablet configuration.

What formulations are protected by claims 7 through 12?

Claims 7 through 12 add a light-stabilizing agent to the oxidation-stabilized formulation.

The permitted light-stabilizing compounds are:

Polyvinylpyrrolidone;
Propyl gallate; and
Alpha-tocopherol.

Claims 8 through 12 narrow the claim set to polyvinylpyrrolidone and L-methionine. Claim 11 requires approximately:

0.02% to 0.03% pergolide mesylate;
0.2% to 0.4% L-methionine; and
1% to 2% polyvinylpyrrolidone.

Claim 12 specifies an approximately 300 mg tablet containing:

Approximately 73 mcg pergolide mesylate;
Approximately 1 mg L-methionine; and
Approximately 4 mg polyvinylpyrrolidone.

This group has a narrower technical footprint than claim 1 because it requires both oxidation and light stabilization. A formulation using methionine but no listed light stabilizer would not fall within claims 7 through 12, although it could have implicated claims 1 through 6 before expiration.

What is the patent's legal status and expiration date?

U.S. patent term

U.S. Patent No. 5,114,948 issued May 19, 1992. Because it is a pre-June 8, 1995 patent, its ordinary term was 17 years from issue rather than 20 years from the earliest effective nonprovisional filing date.[2]

Event	Date
U.S. patent issue	May 19, 1992
Ordinary 17-year expiration	May 19, 2009
Current enforceability	Expired
Current patent barrier to U.S. entry	None

The patent should not be treated as an active U.S. exclusivity right. Any freedom-to-operate analysis must instead consider later patents, regulatory status, trademarks, product-specific approvals, and manufacturing know-how.

What was the FDA and Orange Book relevance?

Pergolide mesylate was marketed in the United States under the Permax brand for Parkinson's disease. The product was associated with FDA New Drug Application No. 018483 and was later withdrawn from the U.S. market after safety concerns involving cardiac valvulopathy.[3]

A formulation patent may be listed in the Orange Book if it claims the drug product, an approved method of use, or another eligible subject matter under FDA listing rules. The presence of a patent in the Orange Book does not extend the patent term. Nor does patent expiration preserve market exclusivity after expiration.[4]

For U.S. regulatory analysis, the relevant conclusions are:

Patent 5,114,948 is expired.
Any former Orange Book listing could no longer create current patent-based delayed ANDA approval.
A Paragraph IV certification against this patent would have been relevant only before expiration.
A post-expiration applicant would not face a current infringement bar from this patent.
The historical withdrawal of Permax affects the commercial route to market, but it does not revive the patent.

When did pergolide lose U.S. patent exclusivity?

Pergolide's exclusivity must be separated into several categories.

Exclusivity type	Relevance to Patent 5,114,948
Active-ingredient patent	Not established by the supplied claims
Formulation patent	Expired May 19, 2009
Method-of-use patent	Not covered by the supplied claims
FDA orphan-drug exclusivity	Not established from the supplied information
NDA exclusivity	Separate from patent term
Trademark exclusivity	Permax trademark rights are separate
Regulatory market availability	Affected by withdrawal of pergolide products

The patent did not claim a new molecular entity. Its value was limited to a specific formulation architecture. A competitor could have avoided the narrowest claims by using a different salt, different antioxidant, different light stabilizer, or a different composition outside the claimed ranges, subject to the broader claims and applicable equivalents doctrine.

How strong was the patent estate for pergolide mesylate?

The estate represented by Patent 5,114,948 was technically focused rather than broad.

Strengths

It addressed a recognized stability problem.
Claim 1 covered pergolide salts generally.
The claim used "comprising," allowing additional ingredients.
The claims covered both composition and method categories.
The formulation examples were closely aligned with a commercial low-dose tablet.

Limitations

The claims required a listed amino-acid stabilizer.
The strongest commercial embodiments were concentrated around L-methionine.
Claims 4, 5, 11, and 12 imposed quantitative restrictions.
The patent did not cover the pergolide molecule itself.
The patent expired in 2009.
The claims were vulnerable to design-around strategies using different stabilization systems, formulations, or dosage forms.

The historical estate was therefore meaningful for the disclosed formulation but weak as a platform estate for the broader pergolide market.

Which companies challenged or could challenge this patent?

No current Paragraph IV litigation can create a live challenge to Patent 5,114,948 because the patent expired in 2009. A historical ANDA applicant could have challenged it through a Paragraph IV certification, sought a noninfringement or invalidity position, or waited for expiration under a Paragraph III certification.

The supplied information does not establish:

The identity of any historical ANDA filers;
Whether a Paragraph IV notice was served;
Whether Eli Lilly or another patent owner filed suit;
Whether a 30-month stay occurred;
Whether the parties entered a settlement;
Whether a terminal disclaimer or reexamination affected the patent.

Accordingly, no named challenger, litigation date, or settlement should be attributed to this patent without a verified court, FDA, or USPTO record.

What generic entry risks remain?

Patent-based entry risk from U.S. Patent 5,114,948 is zero because the patent expired. Residual commercial and regulatory risks are separate.

Formulation and manufacturing risk

A generic manufacturer may still need to address:

Pergolide oxidation during manufacture and storage;
Light sensitivity;
Low-dose content uniformity;
Stability of pergolide mesylate in the selected excipient system;
Tablet segregation and blend uniformity;
Packaging and moisture protection;
Analytical methods for degradation products.

These are technical barriers, not enforceable rights under the expired patent.

Regulatory risk

Pergolide's FDA history creates a separate issue. An applicant would need a legally available regulatory pathway, a reference product or suitable regulatory basis, and compliance with current FDA requirements. The historic withdrawal of Permax may complicate commercial planning even though it does not create patent exclusivity.

Biosimilar risk

Biosimilar analysis is not applicable. Pergolide mesylate is a small-molecule drug, not a biologic. The relevant competitive pathway is an ANDA or another small-molecule regulatory route, not a biosimilar application under the Public Health Service Act.

How does Patent 5,114,948 compare with competing patent strategies?

Patent strategy	Scope relative to 5,114,948	Present status
Pergolide compound patent	Could cover the active molecule or chemical intermediates	Not shown by supplied claims
Pergolide mesylate salt patent	Could cover the salt or preparation method	Not shown by supplied claims
Oxidation-stabilized formulation	Directly covered by 5,114,948	Expired
Light-stabilized formulation	Covered by claims 7-12	Expired
Tablet manufacturing process	May create separate protection	Not identified
Method-of-use patent	Could cover Parkinson's treatment	Not shown by supplied claims
Packaging patent	Could cover light or moisture protection	Not identified

The patent's scope should therefore be treated as one historical formulation layer, not as the complete pergolide patent landscape.

What licensing deals and litigation affected the patent?

The supplied claim text does not establish a licensing transaction, assignment history, litigation docket, settlement agreement, or covenant not to sue. The named patent owner, inventors, assignments, and litigation record must be verified against USPTO assignment records, PACER, and FDA records before being used in a transaction, litigation, or investment analysis.

No licensing right should be inferred merely from the existence of the patent. Likewise, no settlement or Paragraph IV agreement should be inferred from the patent's association with Permax.

Key Takeaways

U.S. Patent 5,114,948 covers pergolide formulations stabilized against oxidation with methionine, cysteine, or cysteine hydrochloride.
Claims 2 through 6 focus on pergolide mesylate and L-methionine, including a 300 mg tablet containing approximately 73 mcg of pergolide mesylate and 1 mg of L-methionine.
Claims 7 through 12 add polyvinylpyrrolidone, propyl gallate, or alpha-tocopherol for light stabilization.
Claims 13 through 17 cover methods of incorporating the oxidation stabilizer.
The patent issued May 19, 1992, and expired May 19, 2009, under the pre-URAA 17-year patent term.
It provides no current U.S. patent barrier to generic pergolide formulation or manufacture.
Pergolide is a small molecule; biosimilar risk does not apply.
Current commercial risk is driven by FDA regulatory status, product withdrawal, formulation performance, and later unverified patent rights rather than Patent 5,114,948.

FAQs

Does U.S. Patent 5,114,948 cover all pergolide mesylate tablets?

No. It covers pergolide mesylate tablets only when the claimed stabilizer and other limitations are present. The broadest relevant claim requires methionine, cysteine, or cysteine hydrochloride in an amount sufficient to stabilize against oxidation.

Can a generic use L-methionine in a pergolide formulation today?

Yes, Patent 5,114,948 no longer prevents that use because the patent expired in 2009. A manufacturer must still satisfy applicable FDA, quality, and safety requirements.

Is claim 6 limited to exactly 73 mcg of pergolide mesylate?

No. Claim 6 uses "approximately," which may permit a reasonable manufacturing range. The analysis would depend on claim construction, product specifications, and the complete formulation.

Did this patent protect the Permax brand name?

No. Patent rights and trademark rights are separate. The patent covered formulation technology; the Permax name was subject to trademark protection.

Does patent expiration eliminate all barriers to a new pergolide product?

No. It eliminates the barrier created by this patent. Regulatory approval, product safety, manufacturing validation, formulation stability, and any later unexpired patents remain separate issues.

References

United States Patent No. 5,114,948, "Stabilized pharmaceutical compositions containing pergolide," issued May 19, 1992.
Patent Term Adjustment and Patent Term, 35 U.S.C. §§ 154, 156, and 173.
U.S. Food and Drug Administration. (2007). FDA public health advisory: Permax (pergolide) withdrawn from U.S. market.
U.S. Food and Drug Administration. (2023). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	627941	⤷ Start Trial
Australia	6485390	⤷ Start Trial
New Zealand	235710	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,114,948

Summary for Patent: 5,114,948