US Patent 4,237,126: Claim Scope, Vecuronium-Type Steroids, Expiration, and Patent Landscape

US Patent 4,237,126 covers acid-addition salts and aqueous pharmaceutical compositions of a narrowly defined class of monoquaternary aminosteroid neuromuscular blockers. The claims center on a 5α-androstane scaffold containing two piperidino substituents, esterified hydroxyl groups, and quaternization of the 16β nitrogen with a methyl, allyl, or propargyl group.

The patent issued on December 2, 1980. Its original 17-year patent term therefore expired on December 2, 1997, absent a term extension. It does not create a current US exclusionary barrier for generic neuromuscular-blocking products.

What drug technology does US Patent 4,237,126 cover?

The patent protects a chemical class related to vecuronium-type aminosteroid neuromuscular blocking agents. The claimed structures contain:

A 5α-androstane steroid nucleus.
Piperidino groups at the 2β and 16β positions.
One or two lower-aliphatic ester groups at the 3α and, where present, 17β hydroxyl positions.
A monoquaternary ammonium group at the 16β nitrogen.
A second nitrogen that may remain tertiary or may be present as an acid-addition salt.
Organic or inorganic counterions.
Injectable aqueous compositions, optionally buffered at approximately pH 3 to 4.5.

The central chemical concept is a monoquaternary aminosteroid rather than the bis-quaternary structure associated with pancuronium.

Core structural limitations

Claim element	Scope
Steroid nucleus	5α-androstane
Nitrogen substituents	2β,16β-dipiperidino
Quaternization site	16β nitrogen
Quaternizing group	Alkyl, alkenyl or alkynyl group of one to about four carbons
Express examples	Methyl, allyl and propargyl
Ester groups	Lower aliphatic acyl groups derived from C1-C6 carboxylic acids
Preferred ester	Acetyl
Counterions	Chloride, bromide, iodide, methyl sulfate, p-toluenesulfonate and other pharmaceutically acceptable anions
Dosage form	Aqueous pharmaceutical composition
Buffer range	About pH 3 to 4.5

The claims are chemically specific. They do not cover every steroidal neuromuscular blocker, every quaternary ammonium steroid, or every formulation containing an aminosteroid.

How are the 30 claims organized?

The claim set has four principal groups.

Claims 1 through 6: Generic acid-addition salts

Claims 1 and 2 establish the broad chemical class. They require an acid-addition salt of a 16β-monoquaternary derivative of the specified dipiperidino androstane scaffold.

Claim 2 narrows the structure through four variables:

Whether the 17β position is free or esterified.
The identity of the 3α and 17β acyl groups.
The identity of the 16β quaternizing group.
The identity of the counterion.

Claims 3 through 6 narrow the class further:

Claim 3 requires at least one acetyl group.
Claim 4 identifies specific anions.
Claim 5 limits the quaternizing group to methyl.
Claim 6 lists permitted acids, including hydrochloric, hydrobromic, hydroiodic, sulfuric, phosphoric, maleic, citric and tartaric acids.

These claims are composition-of-matter claims. A product that falls within the defined molecular structure could infringe without being sold under the same chemical name used in the patent.

Claims 7 through 20: Named salts

Claims 7 through 20 identify individual ester and salt combinations. They include:

Diacetate derivatives.
3α-propionate/17β-acetate derivatives.
3α-butyrate/17β-acetate derivatives.
3α-pivalate/17β-acetate derivatives.
Hydrochloride, hydrobromide, maleate, citrate, phosphate and tartrate salts.
Methyl, allyl and propargyl quaternary substituents.

These claims provide literal protection for specific chemical entities even where a broader genus claim might face validity or claim-construction challenges.

Claims 21 through 24: In situ salt formation

Claims 21 through 24 cover aqueous pharmaceutical compositions in which the acid-addition salt is formed in situ.

The key limitations are:

A neuromuscular-blocking effective amount of the claimed aminosteroid.
Water.
Formation of the acid-addition salt in the aqueous composition.
Optional buffering to approximately pH 3 to 4.5.

Claim 23 identifies the diacetate methylquaternary compound as a preferred active substance. Claims 21 and 24 contain drafting defects, including repetition and an incomplete alternative phrase. Those defects would require interpretation under the patent’s specification and prosecution history.

Claims 25 and 26: Di-anion salt structures

Claims 25 and 26 address a structure containing two pharmaceutically acceptable anions, designated A− and X−. Claim 26 requires the two anions to be the same.

Structurally, these claims appear directed to a compound having both:

A quaternized 16β nitrogen; and
A protonated second nitrogen present as an acid-addition salt.

That produces a dicationic species with two counterions. This is narrower than a simple monoquaternary bromide or iodide salt.

Claims 27 through 30: Repeated aqueous composition claims

Claims 27 through 30 substantially repeat the formulation concept in claims 21 through 24. They cover:

Water-based compositions.
A neuromuscular-blocking effective amount.
Optional buffering to pH 3 to 4.5.
The diacetate methylquaternary compound as a preferred embodiment.

The duplication may reflect amendment history or an attempt to preserve separate claim formats after prosecution.

What compounds are most directly implicated by the claims?

The named compounds show the patent’s intended development program.

Claim	Representative compound class	Commercial relevance
7	Diacetate, 16β-N-methyl, hydrobromide hydrochloride	Closest to the principal methylquaternary lead
8	3α-propionate/17β-acetate, methylquaternary salt	Ester variation
9	3α-acetate, 17β-free, methylquaternary salt	Desacetylated or mono-ester analog
10	3α-acetate, allyl-quaternary analog	Longer unsaturated quaternizing group
11	3α-acetate, propargyl-quaternary analog	Unsaturated quaternary analog
12-20	Alternative acid salts and ester combinations	Solid-state, formulation and salt-screening coverage

The patent is therefore broader than a single marketed presentation. It claims a family of salts and ester variants, while the formulation claims target injectable use.

Does US Patent 4,237,126 cover vecuronium?

The patent covers a vecuronium-related aminosteroid chemical space, but the answer depends on the exact molecular form.

Vecuronium bromide is a monoquaternary steroidal neuromuscular blocker. Its structure is related to the patent’s 2β,16β-dipiperidino-5α-androstane framework. The precise question is whether the marketed active ingredient has:

The ester pattern recited in the relevant claim.
The same 16β quaternizing group.
The required acid-addition state.
The required counterion arrangement.

A monoquaternary bromide that lacks the additional protonated tertiary amine may not fall within every acid-addition-salt claim, particularly claims 25 and 26. Conversely, an aqueous formulation prepared at acidic pH could implicate the formulation claims if the active compound satisfies the structural limitations.

The patent should therefore be analyzed against the exact chemical identity and labeling of the target product, not merely against the generic name “vecuronium.”

When did US Patent 4,237,126 lose exclusivity?

The patent expired on December 2, 1997, based on its December 2, 1980 issue date and the pre-Uruguay Round 17-year term applicable to the patent. [1]

Event	Date
Patent issued	December 2, 1980
Original term	17 years from issue
Basic expiration	December 2, 1997
Current status	Expired
Current blocking value	None as an enforceable US patent right

The patent predates the modern 20-year term measured from the earliest effective nonprovisional filing date. Patent term adjustment generally does not alter the term of patents issued under the old 17-year-from-issue regime.

No current US patent exclusivity should be attributed to US 4,237,126.

What is the Orange Book status of the technology?

The FDA Orange Book separates drug approval, listed patents and regulatory exclusivity. An expired 1980 patent does not provide current Orange Book protection.

Vecuronium bromide products have been approved as injectable neuromuscular blockers, including branded and generic presentations. Generic applicants generally use the abbreviated new drug application pathway for products that reference an approved small-molecule injectable drug. FDA labeling identifies vecuronium bromide as a nondepolarizing neuromuscular blocking agent used as an adjunct to general anesthesia and mechanical ventilation. [2]

The relevant regulatory conclusions are:

US 4,237,126 is too old to create a current Orange Book patent barrier.
Any historical Orange Book listing would have expired with the patent.
Current market entry depends on active manufacturing, quality, labeling and regulatory requirements rather than this patent.
No biosimilar pathway applies because vecuronium bromide is a chemically synthesized small molecule, not a biologic.

Patent listings for later formulations, delivery technologies or different active ingredients must be analyzed separately from US 4,237,126.

What formulation protection does the patent provide?

The formulation claims are directed to aqueous injectable compositions, not to every possible dosage form.

Protected formulation features

The claims require some combination of:

Water as a vehicle.
A neuromuscular-blocking effective amount.
An acid-addition salt of the defined steroid.
In situ salt formation.
Optional buffering at pH 3 to 4.5.

These limitations are commercially relevant because aminosteroid neuromuscular blockers are commonly supplied as sterile parenteral products. A competing product could avoid literal coverage by using:

A different steroid scaffold.
A different ester pattern.
A different quaternizing group.
A nonaqueous presentation.
A formulation outside the claimed pH range, where clinically and chemically feasible.
A salt state that does not satisfy the claimed acid-addition structure.

The expiration of the patent removes the practical litigation risk in the United States, but the claim architecture remains relevant when assessing historical freedom to operate or foreign equivalents.

How strong were the composition-of-matter claims?

The composition claims were stronger than the formulation claims because they reached the active chemical entities themselves.

Strengths

Defined steroid stereochemistry.
Specific substitution at the 2β and 16β positions.
Coverage of multiple ester groups.
Coverage of several quaternizing substituents.
Coverage of multiple pharmaceutically acceptable counterions.
Named species claims that could survive narrowing of broader genus claims.

Vulnerabilities

Several claims depend on broad functional terms such as “pharmaceutically acceptable.”
The claim set contains apparent typographical and grammatical defects.
The acid-addition-salt requirement may exclude related monoquaternary products that are not protonated at the second nitrogen.
The patent does not cover unrelated steroidal blockers such as pancuronium, atracurium, cisatracurium or rocuronium unless their structures independently satisfy the claim limitations.
Salt and ester changes could create noninfringing alternatives, subject to the doctrine of equivalents and the patent’s prosecution history.

Because the patent expired, these strengths and weaknesses have historical rather than current enforcement significance in the United States.

Which companies challenged or competed with the patented technology?

The principal commercial competition came from other neuromuscular blockers rather than from a current patent challenge to US 4,237,126.

Product	Active ingredient	Structural category	Current patent risk from US 4,237,126
Norcuron	Vecuronium bromide	Monoquaternary aminosteroid	Expired patent risk
Pavulon	Pancuronium bromide	Bis-quaternary aminosteroid	Outside the core claim structure
Zemuron	Rocuronium bromide	Monoquaternary aminosteroid with different substituents	Generally outside the claimed scaffold
Tracrium	Atracurium besylate	Benzylisoquinolinium	Outside scope
Nimbex	Cisatracurium besylate	Benzylisoquinolinium	Outside scope
Anectine	Succinylcholine chloride	Depolarizing small molecule	Outside scope

The commercial competitive set has shifted toward generic vecuronium, rocuronium and other established hospital neuromuscular blockers. Market share is driven by hospital formulary decisions, operating-room demand, supply reliability and pricing.

What generic entry risks exist?

For US 4,237,126 itself, the generic entry risk is zero because the patent expired in 1997.

The relevant current risks are regulatory and manufacturing risks:

Sterility assurance for injectable products.
Control of impurities and degradation products.
Consistent quaternary ammonium content.
Accurate assay of the active ingredient and counterion.
Container-closure integrity.
Stability through the labeled shelf life.
Compliance with current FDA drug-product manufacturing requirements.
Availability of qualified suppliers for the steroid intermediate and quaternization steps.

The patent does not create a biosimilar issue. A generic applicant would address the product through the small-molecule abbreviated pathway, subject to the reference product and FDA requirements.

What manufacturing and IP barriers remain?

Although the patent has expired, the synthesis may remain technically demanding. The process requires control of:

Steroid stereochemistry.
Selective esterification at the 3α and 17β positions.
Selective quaternization at the 16β piperidine nitrogen.
Avoidance of over-quaternization.
Removal of residual salts and organic impurities.
Crystallization or isolation of the selected salt form.
Sterile formulation at an acidic pH.

Those issues are manufacturing barriers, not surviving composition-of-matter rights. Later process patents, impurity-control patents or formulation patents could still matter if they remain unexpired, but they are separate from US 4,237,126.

What is the geographic scope of US 4,237,126?

The patent’s enforceable territorial scope was limited to the United States. Foreign protection would have depended on separately filed national or regional counterparts, including any European, Canadian or other filings.

A US expiration did not automatically terminate foreign patents. However, any foreign patent family member would need its own review for:

Filing date.
Grant date.
Patent-term rules.
Supplementary protection certificate status.
National maintenance payments.
Claim differences.
Regulatory term extensions.

The US patent cannot be used to establish freedom to operate in Europe, Japan, Canada or other jurisdictions.

Did the patent create current revenue exposure?

No current revenue stream can be attributed to this patent as an enforceable US asset. Any historical value arose from exclusivity around the underlying aminosteroid technology and related branded products. After expiration, value shifted to:

Generic injectable supply.
Manufacturing efficiency.
Hospital contracts.
Formulary access.
Product reliability.
Regulatory compliance.

A revenue estimate requires product-level sales data and cannot be derived from the patent claims alone.

Key Takeaways

US Patent 4,237,126 covers acid-addition salts and aqueous compositions of a defined 2β,16β-dipiperidino 5α-androstane class.
The claims include ester, quaternizing-group and counterion variations.
Claims 21 through 30 focus on injectable aqueous compositions and in situ salt formation at approximately pH 3 to 4.5.
The patent is chemically related to vecuronium-type monoquaternary neuromuscular blockers.
Exact coverage of vecuronium depends on the marketed molecular form, ester pattern and salt state.
The patent issued December 2, 1980 and expired December 2, 1997.
It provides no current US patent barrier to generic entry.
No biosimilar pathway applies.
Current commercial barriers are primarily regulatory, sterile-manufacturing and supply-chain related.
Foreign patent rights require separate family-level analysis.

FAQs About US Patent 4,237,126

Is US Patent 4,237,126 still active?

No. The patent expired on December 2, 1997 under the applicable pre-1995 17-year term.

Does the patent cover pancuronium bromide?

Generally no. Pancuronium is a bis-quaternary aminosteroid with a different structural configuration from the monoquaternary acid-addition salts claimed in US 4,237,126.

Does US Patent 4,237,126 cover rocuronium bromide?

The claims do not broadly cover all monoquaternary aminosteroids. Rocuronium has a different substitution pattern and would require a limitation-by-limitation comparison. In any event, the US patent is expired.

Are vecuronium bromide products subject to biosimilar competition?

No. Vecuronium bromide is a chemically synthesized small molecule. Competing products use the generic drug approval pathway rather than the biosimilar pathway.

Can an expired patent still matter in a patent landscape?

Yes. It identifies historical claim scope, technical lineage, prior art and possible foreign counterparts. It does not, however, create a current enforceable US exclusionary right.

References

United States Patent and Trademark Office. (1980). U.S. Patent No. 4,237,126: Steroidal muscle relaxants.
U.S. Food and Drug Administration. (n.d.). Vecuronium bromide injection prescribing information. DailyMed.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations. Orange Book.
U.S. Food and Drug Administration. (n.d.). Abbreviated new drug application process. FDA.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
United Kingdom	35667/78	Sep 5, 1978

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	228728	⤷ Start Trial
Austria	921	⤷ Start Trial
Australia	5034879	⤷ Start Trial
Australia	526270	⤷ Start Trial
Canada	1134813	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 4,237,126

Summary for Patent: 4,237,126