United States Patent 4,855,290: Claim Scope, Expiration, and Patent Landscape

U.S. Patent No. 4,855,290 is an issued compound, formulation, and method-of-treatment patent covering substituted quinuclidine derivatives, including stereoisomers, acid-addition salts, pharmaceutical compositions, transdermal delivery systems, and central nervous system treatment methods. The patent issued on August 8, 1989. Assuming no effective patent-term adjustment, terminal disclaimer, or statutory extension, its 17-year term expired on August 8, 2006.[1][2]

The broadest commercial significance is concentrated in the cis- and trans-isomers of the methyl-substituted compound, the hydrochloride salt, transdermal formulations, and methods directed to central cholinergic deficiency, cholinergic hyperfunction, and Alzheimer-type dementia. The patent is now an expired U.S. patent and does not independently block current generic or follow-on development. Later patents covering a specific active ingredient, formulation, manufacturing process, polymorph, salt, or approved use would require separate analysis.

What does U.S. Patent 4,855,290 cover?

The patent claims a genus of substituted quinuclidine compounds represented by formula (I), together with their geometrical isomers, enantiomers, diastereoisomers, racemates, and acid-addition salts.[1]

The claims also cover:

Pharmaceutical compositions containing the compounds.
Oral, rectal, parenteral, insufflation, and transdermal dosage forms.
Transdermal compositions containing a low-molecular-weight fatty acid.
Unit-dose compositions containing approximately 0.5 to 500 mg of active compound.
Methods for treating central nervous system diseases.
Methods for treating central cholinergic deficiency.
Methods for treating cholinergic hyperfunction.
Methods for treating senile dementia of the Alzheimer type.
Specific dosing ranges for oral and parenteral administration.
Co-administration with compounds including physostigmine, tetrahydroaminoacridine, choline, lecithin, piracetam, aniracetam, pramiracetam, oxiracetam, 4-aminopyridine, 3,4-diaminopyridine, and somatostatin.

The textual claim set supplied for analysis contains notation inconsistencies. Claim 1 refers to R1 and R, while dependent claims principally refer to R1 and R2. Claims 23 and 46 also contain apparent drafting or transcription errors. The enforceable scope must be determined from the official patent document, its prosecution history, and any certificate of correction, not from an OCR or manually transcribed claim set.

How many patent claim categories does U.S. 4,855,290 contain?

The 67 claims fall into five principal categories.

Claim category	Claims	Principal subject matter
Chemical compounds	1-16, 67	Substituted quinuclidine derivatives, stereoisomers, salts, and selected stereochemical forms
Pharmaceutical compositions	17-29, 51-56	Carriers, routes of administration, transdermal systems, unit doses, and combinations
General treatment methods	30-44	CNS diseases, cholinergic deficiency, and cholinergic hyperfunction
Alzheimer-type dementia methods	45-50, 57-66	Specific isomers, routes, dosing ranges, and combination therapy
Named compound	67	3-hydroxy-3-mercaptomethyl quinuclidine

The claim set is unusually broad because it combines a chemical genus with formulation and therapeutic-method claims. Its commercial value would have depended on whether a marketed product fell within the preferred methyl-substituted embodiment and whether later patents were obtained for the final clinical formulation.

What compounds are protected by the patent?

Broad compound genus

Claim 1 covers compounds in which the two substituent variables are selected from broad groups that include:

Hydrogen.
Lower alkyl.
Cyclopentyl.
Cyclohexyl.
Phenyl.
Diphenylmethyl or related diphenylmethylol substituents.
Lower alkyl substituted by one or two phenyl groups.

The claim extends to multiple stereochemical forms and acid-addition salts. This creates a large Markush genus. A compound potentially falls within the genus when its structure matches the claimed formula and both substituent positions satisfy the listed R-group definitions.

Preferred substitutions

The dependent claims narrow the genus to selected embodiments:

Claims	R1 or corresponding first substituent	R2 or corresponding second substituent
2, 5-8	Hydrogen	Methyl, phenyl, diphenylmethyl, ethyl, propyl, or related substituents
3, 9-10	Lower alkyl, cyclopentyl, or cyclohexyl	Broad claimed group, including phenyl
4, 11	Phenyl	Phenyl, diphenylmethylol, or diaryl-substituted alkyl
5, 12-16	Hydrogen	Methyl, including cis and trans forms and hydrochloride salts
67	Not specified in the supplied text	3-hydroxy-3-mercaptomethyl quinuclidine

Claims 5 and 12-16 appear to focus on the methyl-substituted compound and its cis/trans forms. Those claims are commercially more specific and easier to design around than claim 1, but their expiration removes the historical blocking effect.

Stereochemical coverage

Claims 12 and 13 distinguish the cis and trans geometrical isomers by the relative melting points of their hydrochloride salts:

Claim 12: lower-melting cis-isomer.
Claim 13: higher-melting trans-isomer.
Claims 15 and 16: corresponding hydrochloride salts.

This drafting approach identifies stereoisomers through a physical property rather than a fully specified three-dimensional structural descriptor. It may create claim-construction issues if melting point varies with hydration, polymorphism, purity, measurement protocol, or salt preparation.

What formulation patents and delivery systems are covered?

The patent does not stop at chemical composition. Claims 17-29 and 51-56 cover pharmaceutical composition categories that could have been used to support product development.

Transdermal formulations

Claim 21 specifically covers a transdermal composition containing:

A claimed compound or pharmaceutically compatible acid-addition salt; and
A low-molecular-weight fatty acid.

This claim is narrower than the general transdermal composition claims but potentially more commercially relevant because it identifies a delivery-enhancing excipient class. A competing transdermal product could attempt to avoid claim 21 by using a different permeation enhancer, a different salt form, a prodrug, a different active ingredient, or a delivery system that does not satisfy the claim limitations.

Claims 19, 32, 35, 38, 41, 44, 47, and 50 separately address transdermal administration. The method claims may require use of a compound within the claimed chemical genus and may also require the specified disease or therapeutic objective.

Unit-dose formulations

Claims 51-53 define unit-dose compositions containing:

Approximately 0.5 to 500 mg of active compound.
A narrower range of approximately 5 to 100 mg.
A further range of approximately 10 to 50 mg.

Claims 55 and 56 narrow those compositions to oral and parenteral administration. The dose limitations do not independently cover every product in those ranges unless the composition also satisfies the underlying compound and carrier limitations.

Combination formulations

Claims 25 and 54 cover compositions containing the claimed compound with one or more additional agents. The listed agents include older cholinergic, nootropic, and neuroactive compounds. These claims would require the presence of the claimed base compound, the additional agent, and the remaining composition limitations.

What therapeutic uses are protected?

The therapeutic claims are divided into broad and disease-specific groups.

Claims	Therapeutic scope
30-32	CNS diseases generally
33-35	Central cholinergic deficiency using the methyl-substituted embodiment
36-38	Cholinergic hyperfunction using compounds with larger substituents
39-44	Cholinergic hyperfunction using selected diphenylmethyl or methyl/phenyl embodiments
45-50	Senile dementia of the Alzheimer type using specified stereoisomers
57-66	Alzheimer-type dementia with oral or parenteral dose ranges and optional combination therapy

The claims distinguish between two pharmacological directions:

Cholinergic deficiency, associated with the Alzheimer-type claims and the methyl-substituted compound.
Cholinergic hyperfunction, associated with larger substituents such as propyl, cyclopentyl, cyclohexyl, phenyl, or diaryl-substituted groups.

Claims 45-50 are narrower because they identify the Alzheimer indication and particular stereochemical forms. Claims 57-66 add route and dose limitations:

Route	Claimed dose range
Oral, claim 57	Approximately 0.1-60 mg/kg
Oral, claims 58-59	Approximately 0.5-10 mg/kg; then 1-5 mg/kg
Parenteral, claim 62	Approximately 0.01-40 mg/kg
Parenteral, claims 63-64	Approximately 0.05-5 mg/kg; then 0.1-2 mg/kg

The practical enforceability of these method claims would have depended on the approved indication, labeling, prescribing behavior, and evidence that a provider or patient practiced all required limitations.

When did U.S. Patent 4,855,290 lose exclusivity?

U.S. Patent 4,855,290 issued on August 8, 1989. For a pre-June 8, 1995 U.S. patent, the ordinary term was 17 years from grant, subject to statutory exceptions.[2][3]

Event	Date or result
Patent issuance	August 8, 1989
Ordinary 17-year expiration	August 8, 2006
Current status	Expired by term
Patent-term extension relevance	No extension is established from the supplied record
Current blocking effect	None from this patent alone

A patent expiration analysis should still check the USPTO patent file for terminal disclaimers, reexamination certificates, certificates of correction, and any other recorded event affecting the claims. None of those events can revive an expired ordinary patent term after its statutory expiration.

What is the Orange Book status of U.S. 4,855,290?

U.S. Patent 4,855,290 is not, by itself, evidence of an active Orange Book-listed patent. The FDA Orange Book lists patents associated with approved drug products, including patents submitted by an NDA holder and accepted for listing under FDA procedures.[4]

The patent’s 1989 issue date and 2006 expiration date make it commercially unlikely to be an active Orange Book barrier today. The supplied record does not identify:

An NDA number.
An approved product name.
An FDA-listed active ingredient.
A current Orange Book patent entry.
A patent-use code.
A Paragraph IV certification or litigation notice tied to this patent.

A generic applicant facing an active listed patent would ordinarily address it through a Paragraph IV certification or a certification that the patent will not be infringed, is invalid, or is unenforceable. Because this patent has expired, a current ANDA would not need to make a Paragraph IV challenge to defeat its remaining term.[5]

Which companies challenged or litigated this patent?

The supplied patent and claims do not establish a current Paragraph IV case, infringement action, settlement, or license involving U.S. Patent 4,855,290. No litigation or settlement should be attributed to this patent without a verified PACER, court docket, USPTO, or FDA record.

The likely historical commercial risk would have arisen from:

A generic compound matching the claimed methyl-substituted quinuclidine.
A transdermal product using a low-molecular-weight fatty acid.
An Alzheimer treatment using the claimed cis or trans hydrochloride salt.
A product using the patented dosage and route combinations before August 8, 2006.

After expiration, any continuing market dispute would more likely concern later patents, regulatory exclusivity, trade secrets, manufacturing know-how, or product-specific patents rather than this patent.

How strong was the patent estate?

Strengths

The patent had several structural strengths during its term:

Claim 1 created a broad chemical genus.
The claims expressly covered stereoisomers and acid-addition salts.
Dependent claims identified commercially useful methyl and phenyl embodiments.
Formulation claims covered multiple administration routes.
Claim 21 targeted a transdermal composition with a defined enhancer class.
Method claims addressed both broad CNS treatment and Alzheimer-type dementia.
Dose claims provided additional fallback positions.

Weaknesses

The patent also presents potential vulnerabilities:

The supplied claims contain inconsistent R-group terminology.
Several claims appear to use “diphenylmethylol” where a different chemical term may have been intended.
Claims 45-47 contain inconsistent references to the cis and trans claims.
Broad Markush claims could face written-description, enablement, novelty, or obviousness challenges depending on the prior art and specification examples.
Treatment claims may raise issues concerning disease definition, clinical proof, and divided infringement.
Melting-point definitions for cis and trans salts may be vulnerable to analytical variation.
Broad composition claims could be narrowed by the requirement for a compatible salt, inert carrier, or specified dosage form.

The patent’s current strength is therefore historical rather than exclusionary. Its term has expired, and any business value now lies in freedom-to-operate history, prior-art mapping, or identification of later patent families.

What manufacturing and intellectual-property barriers remain?

The expired patent does not remove all potential barriers to commercial development. Relevant surviving barriers may include:

Barrier	Potential impact
Later compound patents	Could cover a specific active ingredient, salt, stereoisomer, or analog
Process patents	Could cover synthesis, purification, resolution, or salt formation
Formulation patents	Could cover patches, permeation enhancers, release profiles, or excipient systems
Polymorph patents	Could cover a defined crystalline form or hydrate
Regulatory exclusivity	Could delay approval even without an unexpired patent
Trade secrets	Could protect manufacturing parameters not disclosed in the patent
Clinical and CMC requirements	Could create substantial development cost for an unapproved compound
Foreign patents	Could remain relevant in jurisdictions with different filing, term, or lapse histories

There is no biosimilar pathway issue for a conventional small-molecule quinuclidine compound. A follow-on product would ordinarily use an ANDA, 505(b)(2), or full NDA pathway depending on the reference product, formulation, clinical evidence, and FDA reference listed drug status.[4][6]

How does this patent compare with a modern drug patent estate?

U.S. 4,855,290 is broader in chemical and therapeutic language than many modern product patents, but it is less specialized in several areas now used to extend market exclusivity.

Estate element	U.S. 4,855,290	Modern product estate
Base compound	Broad Markush genus	Often supported by composition-of-matter and species patents
Stereochemistry	Cis/trans claims	Usually defined by structural nomenclature and analytical data
Formulation	General routes, unit dose, transdermal fatty acid	Device, release profile, excipient, and manufacturing claims
Method of use	CNS, cholinergic disorders, Alzheimer dementia	Label-specific and biomarker-defined indications
Manufacturing	Limited in supplied claims	Often separate process, purification, and solid-form patents
Regulatory linkage	No current evidence of active listing	Frequently coordinated with Orange Book listing
Term strategy	Expired in 2006	Often supported by patent-term adjustment, extension, and continuation filings

The patent is best understood as an early platform patent. It attempted to capture the chemical series, preferred stereoisomers, formulations, routes, and therapeutic uses in one filing. Its principal limitation today is expiration, not narrow claim drafting.

What generic launch scenarios exist?

A generic or follow-on developer would generally face three historical scenarios.

Small-molecule generic before expiration

Before August 8, 2006, a product matching the claimed compound or salt could have faced infringement risk under claims 1, 5, 12-16, or 67. A transdermal product could also have faced claims 19, 21, 32, 35, 38, 41, 44, 47, or 50.

Launch after expiration

After August 8, 2006, the patent no longer prevented manufacture, sale, or use of a covered compound in the United States. The developer would still need to address any later patents and FDA requirements.

Alternative compound or formulation

A developer could have designed around the patent by changing:

The core scaffold.
The R-group combination.
The stereochemical form.
The salt or solid form.
The permeation enhancer.
The dosage form.
The therapeutic indication.
The manufacturing route.

Design-around analysis must be performed against each asserted claim, not against the patent title or the broad chemical concept.

Key Takeaways

U.S. Patent 4,855,290 covers substituted quinuclidine compounds, their stereoisomers and salts, formulations, transdermal systems, and CNS treatment methods.
The central commercial embodiments are the methyl-substituted cis and trans isomers, particularly their hydrochloride salts.
Claims 21 and related method claims specifically address transdermal delivery and low-molecular-weight fatty acid enhancers.
Claims 45-66 focus on Alzheimer-type dementia, dose ranges, routes of administration, and combination therapy.
The patent issued August 8, 1989 and ordinarily expired August 8, 2006.
It is not an active U.S. patent barrier today.
No Paragraph IV challenge, settlement, license, or litigation should be attributed to this patent without a verified docket or regulatory record.
The most important current FTO questions concern later patents covering a specific active ingredient, salt, polymorph, formulation, process, or approved product.

FAQs About U.S. Patent 4,855,290

Does U.S. Patent 4,855,290 cover both cis and trans compounds?

Yes. Claims 12-16 separately identify lower- and higher-melting geometrical isomers and the corresponding hydrochloride salts. The claim language identifies them as cis and trans forms.

Does the patent cover a transdermal patch?

Potentially. Claims 19 and 21 cover transdermal compositions, and claim 21 requires a claimed compound or salt together with a low-molecular-weight fatty acid. A patch would need to satisfy every applicable claim limitation.

Is claim 67 an independent compound claim?

Yes. As supplied, claim 67 separately recites 3-hydroxy-3-mercaptomethyl quinuclidine. Its precise scope depends on the official claim text and structural definition in the issued patent.

Can a company rely on the patent’s expiration to launch a product?

The expiration eliminates this patent as a current U.S. patent barrier. A launch still requires review of later patents, FDA approval requirements, regulatory exclusivity, manufacturing rights, and any foreign patent rights.

Is there a biosimilar pathway for the claimed compounds?

No. The claimed compounds are conventional small molecules, not biologic products. A follow-on developer would generally evaluate an ANDA, 505(b)(2), or NDA pathway rather than the biosimilar pathway.

References

U.S. Patent No. 4,855,290. (1989). United States Patent and Trademark Office.
United States Code, 35 U.S.C. § 154. Patent term and adjustment.
Manual of Patent Examining Procedure § 2710. United States Patent and Trademark Office.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
United States Code, 21 U.S.C. § 355(j). Abbreviated applications for new drugs.
U.S. Food and Drug Administration. (2024). Applications covered by section 505(b)(2).

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Israel	75166	May 10, 1985
Israel	77568	Jan 10, 1986

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	242213	⤷ Start Trial
Austria	83485	⤷ Start Trial
Australia	599610	⤷ Start Trial
Australia	6485986	⤷ Start Trial
Canada	1311479	⤷ Start Trial
Germany	3687288	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 4,855,290

Summary for Patent: 4,855,290