Details for Patent: 5,155,268

Summary for Patent: 5,155,268

Title:	Antiarrhythmic N-aminoalkylene alkyl and aryl sulfonamides
Abstract:	The present invention provides novel sulfonanilide and benzene-alkylaminium compounds which are the products of processes utilizing novel intermediates. Both the novel compounds and the novel intermediates are useful for the therapeutic or prophylactic treatment of arrhythmic activity.
Inventor(s):	Jackson B. Hester, Jr.
Assignee:	Pharmacia and Upjohn Co
Application Number:	US07/423,499
Patent Claim Types: see list of patent claims	Compound;

United States Patent 5,155,268 (Scope, Claims Construction, and US Patent Landscape for N,N-Diethyl-N-Heptyl Hydroxy Benzeneethanaminium Bromide and Related Methanesulfonamide Salts)

Executive summary: US Patent 5,155,268 claims a narrow, specific set of cationic hydroxy-alkylene amines as quaternary ammonium bromide salts and a related pair of methanesulfonamide hydroxy-alkylene intermediates. The claim set is tight around defined positional hydroxy isomers (β/δ/γ on the carbon chain), the defined aryl substituent (4-(methylsulfonylamino)benzyl/alkyl anilines in specific side-chain lengths), and the counterion (bromide) for the quaternary ammonium species. The most relevant landscape risk is not broad method-of-use coverage but design-around around (i) the counterion, (ii) the hydroxy position (β vs γ vs δ), and (iii) the precise alkyl chain identity (notably N-ethylheptyl substitution) and side-chain length for the quaternary ammonium.

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What exactly does US Patent 5,155,268 claim: compound coverage, isomers, and salts?

US 5,155,268 is directed to discrete chemical entities, not a broad genus formulation. The two independent claim concepts you quoted split into:

1. Claim 1: quaternary ammonium bromide salts with a hydroxy group on a defined carbon position and an aryl ring bearing a methylsulfonylamino substituent and an aniline-linked side chain of a defined length.
2. Claim 2: “hydroxy-alkylene compound[s]” and pharmaceutically acceptable salts, covering two methanesulfonamide-substituted hydroxy-alkylene structures.

Claim 1: three positional hydroxy isomers of the same quaternary ammonium skeleton

Claim 1 defines “the compound selected from the group consisting of” three named quaternary ammonium bromide compounds:

• (a) N,N-diethyl-N-heptyl-β-hydroxy-4-[(methylsulfonyl)amino]benzeneethanaminium bromide
• (b) N,N-diethyl-N-heptyl-δ-hydroxy-4-[(methylsulfonyl)amino]benzenebutanaminium bromide
• (c) N,N-diethyl-N-heptyl-γ-hydroxy-4-[(methylsulfonyl)amino]benzenepropanaminium bromide

Scope implications:

• The phrasing “selected from the group consisting of” is a classic closed list. A literal infringement theory generally needs the accused compound to match one of the three recited structures.
• The hydroxy position is not interchangeable. The patent differentiates β, γ, δ and also ties those positions to specific side-chain lengths:
  • β-hydroxy pairs with ethanamine (two-carbon chain from the benzene linkage),
  • γ-hydroxy pairs with propanamine (three-carbon chain),
  • δ-hydroxy pairs with butanamine (four-carbon chain).
• The counterion is bromide, stated explicitly. If an accused compound is the same cation with a different pharmaceutically acceptable counterion (chloride, tosylate, methanesulfonate), literal coverage for the “bromide” language is not automatic.

Claim construction pressure points likely to matter in litigation:

• Whether “benzeneethanaminium” means a specific linkage pattern and carbon count rather than a functional equivalent.
• Whether the hydroxy substitution is exactly at the β/γ/δ carbon relative to the ammonium nitrogen and benzene linkage.
• Whether stereochemistry (not shown in the text you provided) exists in the spec and if it is required for the claimed compounds.

Claim 2: hydroxy-alkylene methanesulfonamides (two specific alternatives)

Claim 2 covers:

• “A hydroxy-alkylene compound and pharmaceutically acceptable salts thereof which is (a) N-(4-(4-(ethylheptylamino)-1-hydroxybutyl)phenyl)methanesulfonamide; or (b) N-(4-(4-dibutylamino)-1-hydroxybutyl)phenyl)methanesulfonamide.”

Scope implications:

• This is also a closed set (“which is (a) …; or (b) …”).
• It is aimed at methanesulfonamide derivatives with a 1-hydroxybutyl chain on a substituted phenyl.
• Two variants are present:
  • One includes an ethylheptylamino substituent.
  • The other includes a dibutylamino substituent.
• The claim language includes “pharmaceutically acceptable salts,” which broadens coverage relative to claim 1’s explicit bromide, because claim 2 is not limited to one counterion class.

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How narrow is the claim scope: literal infringement vs “equivalents” in US practice?

Literal scope is narrow. Both claims rely on named, specific chemical structures and/or closed lists. That structure limits literal reach to compounds that are the same (or include the same essential structural elements as recited).

Equivalents risk is still present but constrained.

• Even if an accused compound has the same core chemical function, prosecution history estoppel and prior art constraints often narrow “equivalents,” especially for early chemical claims that are drafted as explicit structural lists.
• Substituting the counterion for claim 1 is a frequent design-around; if the spec emphasizes bromide specifically, a counterion change can weaken equivalents arguments.

Net effect: the patent is most valuable as a direct hit for compounds that match the claim structures, and less powerful against “nearby” analogs unless the specification supports broader definitions that the claims do not.

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What patents likely surround US 5,155,268: typical chemical families and risk areas?

Without the full patent text (spec claims, dependent claims, and citations), the analysis of surrounding patents is constrained to structural landscape expectations based on the claimed chemical motifs. The claim set points to a chemical family containing:

1. Quaternary ammonium hydroxy-alkylene derivatives (claim 1) with:
   • N-substitution described as diethyl + heptyl and
   • defined hydroxy positions tied to side-chain length.
2. Aryl methanesulfonamide hydroxy-alkylene scaffolds (claim 2), likely intermediates or related active scaffolds.

Landscape hot spots that typically cluster around these motifs

• Hydroxy-alkylene positional isomer patents: β/γ/δ variants are often claimed separately across families.
• Counterion and salt form coverage: quaternary ammonium drugs frequently have follow-on claims for different salts to capture commercial supply.
• Side-chain length changes (ethanamine vs propanamine vs butanamine): structurally close but often patented separately.
• N-substitution changes: replacing heptyl with other alkyls or changing diethyl to other dialkyl combinations.

If an active is commercialized, follow-on filings often target:

• improved crystalline forms,
• specific salt forms,
• controlled release formulations,
• process improvements for making the quaternary ammonium compounds.

The claim set you provided does not, by itself, suggest broad process or formulation coverage, so the practical enforcement terrain is likely compound-level rather than formulation-level.

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When does US 5,155,268 lose exclusivity: how to treat this in a generic entry timeline?

US chemical patents typically have:

• a 20-year term from the earliest effective non-provisional filing date plus adjustments, subject to patent-specific details.

You have not provided filing date, priority, or any PTA/APIB facts. With only the patent number and claim text, a precise exclusivity expiration calculation is not possible to state as a fact. The correct business use here is to treat 5,155,268 as a hard compound patent and to evaluate generics through:

• Orange Book status (if any NDA listed for the active),
• whether later patents extend exclusivity for formulations, polymorphs, or method-of-use,
• whether Paragraph IV challenges were filed against later listed patents rather than 5,155,268 itself.

Given the chemical specificity, commercial risk often comes from later secondary patents even if 5,155,268 is near or past expiry.

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What does the patent family likely cover beyond these two claims: dependents, intermediate coverage, and process?

The claim excerpt indicates at least two independent claim groupings. Chemical patents like this usually include additional claims that can be important for infringement strategies:

• dependent claims narrowing within each recited structure,
• additional salt forms,
• stereochemical embodiments,
• intermediates used to make the claimed quaternary ammonium or methanesulfonamide.

However, you have not provided the complete claim set. For infringement or freedom-to-operate (FTO) mapping, the critical question is whether the spec introduces broader definitions that could be read into the claims, or whether dependent claims cover additional variants that would block straightforward substitutes.

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What generic entry risks exist for compounds “close” to the claim structures?

Design-around levers for claim 1 (quaternary ammonium bromides)

• Counterion swap: Replace bromide with another counterion. Because bromide is explicit in claim 1, this is often a direct literal workaround.
• Hydroxy positional change: Move the hydroxy substitution from β to γ or δ with corresponding chain-length differences. Because the claim list is closed to three positional isomers, changing position can avoid literal coverage.
• Side-chain length change: Use a different alkylene chain length, e.g., change the “ethanaminium” to “propanaminium” or “butanaminium” pattern not matching the claimed mapping.
• N-substitution change: Alter the alkyl pattern (heptyl or diethyl) to another alkyl distribution.

Design-around levers for claim 2 (methanesulfonamide hydroxy-alkylene)

• Change the amine substitution on the side-chain: move from ethylheptylamino to another N-substituent not equal to the stated groups.
• Change the hydroxybutyl arrangement: alter carbon count or position relative to the phenyl.

Commercially, companies often adopt one of these levers while keeping pharmacology and ADME similar.

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How strong is the patent estate for the claimed scaffold: enforceability and claim breadth signals?

Based on the claim language you provided:

• Breadth: Low to moderate. The claims are specific. There is no “generic formula” you quoted.
• Clarity of essential elements: High. The named components and positions are explicit.
• Potential enforceability profile: Strong for exact-match competitors; weaker against analogs that make even minor structural changes that fall outside the closed list.

For investors and litigators, the key signal is that the patent’s value is likely concentrated in enforcement against copycat synthesis of the exact cationic bromides or the exact methanesulfonamide hydroxybutyl derivatives.

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What patent litigation patterns would matter for this type of US chemical patent?

For scaffold-specific chemical patents, litigation typically centers on:

• whether the accused compound has the same counterion and positional hydroxy structure,
• whether the accused compound’s side-chain length and N-substitution match the named structure,
• claim construction disputes over how to map “β/γ/δ” onto the drawn/defined skeleton.

If the patent is enforced, the plaintiff usually uses:

• expert chemical comparison,
• evidence of accused product identity and salt form,
• infringement under Markman constructions of the β/γ/δ mapping.

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Key Takeaways

• US 5,155,268 is a structure-defined US chemical patent with closed-list claim scope in the text you provided.
• Claim 1 is limited to three specific N,N-diethyl-N-heptyl hydroxy benzene amino quaternary bromide isomers, each tied to a corresponding side-chain length and hydroxy position (β/δ/γ).
• Claim 2 is limited to two methanesulfonamide hydroxy-alkylene structures, including ethylheptylamino and dibutylamino variants, with coverage extending to pharmaceutically acceptable salts.
• The most practical design-around levers are counterion substitution (especially for claim 1), hydroxy positional changes, and altering N-alkyl identity or side-chain length.
• The claim language suggests enforcement strength against exact-match compounds and weaker coverage for near analogs.

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FAQs

1) What happens if a competitor sells the same quaternary ammonium cation as claim 1 but with a non-bromide counterion?
Claim 1’s explicit “bromide” language makes a counterion change a primary literal design-around route.

2) Do the β, γ, and δ hydroxy positions in claim 1 create separate protected embodiments?
Yes. The claims list each positional isomer as a distinct alternative within a closed “group consisting of” limitation.

3) Does claim 2 cover only the two named methanesulfonamide compounds or a broader class?
It covers only the two named alternatives, with additional breadth limited to “pharmaceutically acceptable salts” of those compounds.

4) Are intermediates or process steps covered by the claims you provided?
Not from the excerpt. The provided claims are directed to specific final chemical entities rather than process/intermediate steps.

5) What commercial products would be most at risk under US 5,155,268?
Products containing one of the three claim 1 quaternary ammonium bromide isomers or one of the two claim 2 methanesulfonamide hydroxy-alkylene derivatives, marketed in forms that preserve the claimed structural elements (including the bromide for claim 1).

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References

1. US Patent No. 5,155,268. (claims as provided in prompt).

Drugs Protected by US Patent 5,155,268

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate

International Family Members for US Patent 5,155,268

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0164865		SPC/GB97/003	United Kingdom
European Patent Office	0164865		C970030	Netherlands
European Patent Office	0164865		97C0044	Belgium
Germany	3566886