Details for Patent: 5,578,610

Summary for Patent: 5,578,610

Title:	Piperidine derivatives
Abstract:	The present invention relates to substantially pure piperidine derivative compounds of the formulae: ##STR1## wherein R1 is hydrogen or hydroxy;R2 is hydrogen;or R1 and R2 taken together form a second bond between the carbon atoms bearing R1 and R2 ;R3 is --COOH or --COOR4 ;R4 has 1 to 6 carbon atoms;A, B, and D are the substituents of their respective rings each of which may be different or the same and are hydrogen, halogens, alkyl, hydroxy, alkoxy, or other substituents.A process of preparing such piperidine derivative compounds in substantially pure form is also disclosed.
Inventor(s):	Thomas E. D'Ambra
Assignee:	Aventis Pharmaceuticals Inc , Curia Global Inc
Application Number:	US08/456,273
Patent Claim Types: see list of patent claims	Use; Composition;

Patent 5,578,610 (US 5,578,610) Scope, Claim Coverage, and U.S. Patent Landscape for Piperidine/“Piperidine Derivative” Antiallergic Compounds

US 5,578,610 has broad U.S. claim coverage around a class of substantially pure piperidine (and piperidine-derived) compounds defined by a set of core substitution rules (generic R-group framework), plus downstream coverage for salts, pharmaceutical compositions, and use in allergic-reaction treatment. Independent coverage also extends to a process genus for preparing substantially pure regioisomers of the same compound class, using halogenated acylation and/or organometallic-type coupling and regioisomer purification steps. The risk profile for competitors is driven by (1) the genus breadth of chemical scope, (2) “substantially pure” and “substantially pure regioisomer” qualifiers that can be contested in infringement/validity, and (3) process-claim availability even where a competitor sources or synthesizes via an alternative route.

What does US 5,578,610 claim, and how broad is the chemical genus under R1–R4 and ring substituents A, B, D?

Executive scope snapshot (by claim type)

• Product (compound) claims: Claims 1–7 cover “substantially pure” piperidine derivative compounds in a generic structural framework, with additional dependent claim formulae narrowing to specific member structures.
• Salt coverage: Claim 1 explicitly covers “or a salt thereof.”
• Formulation claims: Claims 8–10 cover pharmaceutical compositions including carrier plus the compound, including “consists essentially of” forms.
• Method-of-use claims: Claim 11 covers treating allergic reactions via administering the claimed composition.
• Process claims: Claims 12–17 cover preparing the piperidine derivatives via regioisomeric starting material preparation, acylation/hydrolysis/regioisomer recovery, and halogenation/reaction to install piperidine moieties (or coupling to a piperidine reagent).

Core claim language that drives breadth

Claim 1 is the main independent chemical genus claim. It anchors the compound to:

• A piperidine derivative defined by a formula (not reproduced in text here), with substituent rules:
  • R1: hydrogen or hydroxy, or R1 and R2 together form a second bond between carbon atoms bearing R1 and R2 (ring-closure feature).
  • R2: hydrogen (subject to the fused bond condition above).
  • R3: –COOH or –COOR4 (carboxylic acid or alkyl ester).
  • R4: alkyl C1–C6 (ester side-chain breadth).
  • A, B, D: each independently can be hydrogen, halogens, alkyl, hydroxy, or alkoxy (independent positions, multiple permutations).
• Coverage for “substantially pure” compounds and their salts.

This structure gives competitors several “escape” angles that still remain within claim scope for functional equivalence:

• Changing ester alkyl group within C1–C6 remains within claim 1.
• Introducing ring substituents within H/halogen/alkyl/hydroxy/alkoxy remains within claim 1.
• Forming the R1/R2 fused second bond is optional via the claim’s alternative definition.

Dependent claims 2–7: what they typically do in practice

Claims 2–7 each state a “substantially pure piperidine derivative” “wherein the compound has the formula” for specific enumerated structures (STR42–STR48 placeholders). In infringement terms, those dependent formulas usually:

• Lock onto specific substituent combinations and/or specific regioisomeric member(s) of the genus.
• Create a fallback position for the patentee if the broad genus is narrowed by claim construction, prior art, or prosecution history.

Claim 8–11: composition and method coverage

• Claim 8: pharmaceutical composition = carrier + compound of claim 1.
• Claim 10: “consists essentially of” the compound and carrier (limits additional actives but leaves typical excipients).
• Claim 11: method of treating allergic reactions in a patient by administering that composition.

What is “substantially pure” doing to claim boundaries?

Across claims 1–7 and the process claims (12), “substantially pure” and “substantially pure regioisomer” are critical. In litigation, those terms typically determine whether:

• An accused compound is merely present as part of a mixture versus being purified sufficiently.
• Purification and isomeric content in commercial practice can be contested. In practical landscape terms, “substantially pure regioisomer” also pushes the scope toward products that are marketed/supplied as enriched regioisomer forms rather than equilibrated isomer mixtures.

Which patents or claim families usually surround US 5,578,610’s piperidine-antiallergic space?

Only the claim text is provided here, without file history, listed references, or patent family data. With that limitation, a complete, accurate “all patents in the family / all continuations / all related continuations” landscape cannot be produced.

How does US 5,578,610 overlap with generic and competitor design-around strategies (esters, salts, and regioisomers)?

1) Ester vs acid: R3 is locked to “–COOH or –COOR4”

Because claim 1 explicitly includes carboxylic acid and C1–C6 esters, competitors cannot avoid coverage by switching between acid and simple lower alkyl ester forms. Only moving to:

• a different acyl functionality outside –COOH/–COOR4, or
• an ester with chain length outside C1–C6, can reduce overlap at the claim 1 level.

2) R4 range (C1–C6) is a defined “safe harbor” only outside that band

Within C1–C6, ester selection remains covered. If a competitor uses longer chain esters, that can become a non-infringing argument depending on exact claim interpretation and formula mapping.

3) Salt form risk

Claim 1 covers “or a salt thereof.” Many “salt-only” design-arounds fail because salt selection usually does not change the core compound identity. The main question becomes whether the accused product is genuinely a salt of the claimed compound versus a different chemical entity.

4) Ring substituent permutations (A, B, D)

A/B/D each allow H, halogen, alkyl, hydroxy, alkoxy. That is a wide permissive set. Design-around by substituting:

• other heteroatoms (beyond hydroxy) such as amines, nitriles, sulfonamides,
• or different substitution patterns not captured by the definitions, may fall outside the claim’s A/B/D allowed set, but only if the accused structure cannot be mapped into the allowed categories.

5) “Substantially pure regioisomer” creates a mixture-related pathway

Process and product claims both emphasize regioisomer purity. A competitor may attempt to market a mixture with regioisomer distribution below the threshold implied by “substantially pure.” The success of that strategy depends on:

• the actual isomeric composition in commercial lots,
• analytical methods and vendor specs,
• and the claim construction approach adopted in litigation.

What do the process claims (12–17) cover, and how hard is it to “carve around” via alternate synthesis?

US 5,578,610 includes a process genus aimed at preparing the same compound class via:

• providing a substantially pure regioisomer (of a “formula” with R3 and A substituents),
• converting it with a piperidine compound under conditions that form the targeted piperidine derivative.

Claim 12: overall process genus

Claim 12 broadly covers:

• starting from a substantially pure regioisomer of a defined scaffold (with R3 and A substituents),
• converting with a piperidine compound of another defined scaffold (with R1/R2 features and B/D substituents),
• under conditions effective to form the resulting formula in which the piperidine derivative is formed.

This claim is likely to be litigated in one of two ways:

• As an infringement-by-process if the end product matches and the accused process steps are similar enough to satisfy claim limitations.
• As a non-infringement defense if the accused process uses different intermediates, lacks the substantially pure regioisomer step, or does not “converting … under conditions effective to form” the claimed compound via the required transformation.

Claims 13 and 15: acylation + regioisomer mixture formation + hydrolysis + recovery

Claims 13 and 15 specify a providing step that includes:

• acylating a starting compound with a halogen-X species (Claim 13 includes X = halogen),
• producing a first mixture of regioisomers,
• hydrolyzing the mixture to form a second mixture of regioisomers,
• recovering the substantially pure regioisomer of the specified formula.

This is a common pattern for regioisomer purification strategies. To avoid these limitations, a competitor would need to:

• use a different transformation sequence that does not include the “first mixture then hydrolysis then recovery” pattern as claimed, or
• avoid the “substantially pure regioisomer recovery” step as a distinct process step.

Claim 14: acylation using broader coupling activators

Claim 14 expands the acylation partners to include halogen and also organometallic/coupling-activator type groups:

• X1 is a halogen, trialkyl tin, triflate, or substituents useful in organometallic coupling reactions, leading to substantially pure regioisomer formation.

This makes the process claim more difficult to avoid through changes in leaving groups/coupling activators.

Claims 16–17: halogenation + intermediate formation, or direct reaction

• Claim 16: halogenate the substantially pure regioisomer to form a first intermediate compound, then react with a piperidine compound to form the piperidine derivative.
• Claim 17: directly react the substantially pure regioisomer with the piperidine compound.

If a competitor synthesizes by a different chemistry that does not match halogenation/intermediate coupling or does not use substantially pure regioisomer as the direct electrophile partner, infringement risk declines.

What is the infringement exposure profile by product type: API, salts, and combination products?

API exposure

If the marketed active is a substantially pure member within claim 1’s structure rules, the main risk is direct product infringement under claims 1–7.

Salt exposure

Because claim 1 includes salts, API salt forms are typically captured when the salt is of the claimed compound.

Formulation exposure

• Claim 8 captures any pharmaceutical composition containing the claimed compound plus carrier.
• Claim 10 caps “consists essentially of” formulations: if a competitor uses additional active ingredients, they may reduce overlap with claim 10 but still fall under claim 8 unless claim 8 also has an “essentially of” restriction (it does not in the provided text).

Method-of-use exposure

Claim 11 captures administration for allergic reaction treatment. If competitors market the drug for a different indication, risk can shift from method claims to product claims. If the same composition is nonetheless used for allergic reactions, method-of-use risk returns.

When does US 5,578,610 expire in the U.S., and how does that affect generic or biosimilar timing?

Only claim text is provided, not the filing date, patent grant date, priority, or any patent term adjustment data. Without those, a precise exclusivity/expiration schedule cannot be calculated accurately.

What Paragraph IV or ANDA litigation is tied to US 5,578,610?

No litigation docket, ANDA numbers, Orange Book listings, or settlement agreements are provided. A litigation landscape cannot be produced from the claim text alone.

How strong is the patent estate for this chemical class: claim scope vs likely validity attack points?

Even without citations/prior art lists, US 5,578,610’s risk/strength profile is structurally inferable:

Potential validity pressure points

• Genus breadth: Claim 1 allows wide variability in A/B/D substituents and in ester side chains C1–C6, which can raise enablement/breadth questions depending on disclosure adequacy.
• “Substantially pure” / regioisomer qualifiers: These terms can be attacked as vague or as limiting in an unpredictable way during claim construction, affecting both infringement and validity.
• Process genus (12–17): Broad process steps may be vulnerable to prior art process variations unless the specification provides clear, distinguishing features.

Potential patentee advantages

• Specific chemical framework: Even with broad substituent sets, the core scaffold and the piperidine pairing requirements are defined.
• Regioisomer purity emphasis: If the specification taught and enabled a specific regioisomer purification concept and associated members, that can support novelty and non-obviousness.

Key comparison: what would be “closest competitors” to this patent claims-wise?

Given the R-group constraints, the closest competitors are compounds that:

• are piperidine derivatives matching the same core scaffold,
• have R3 = –COOH or C1–C6 ester,
• fall within allowed A/B/D substituent categories,
• are supplied as “substantially pure” regioisomer/enriched products.

Closest-scope competitors likely differ only by:

• ester chain length within or outside C1–C6,
• A/B/D substituent selection within allowed categories,
• salt form.

Key Takeaways

• US 5,578,610 is a broad genus patent for substantially pure piperidine derivatives defined by strict R-group rules: R3 is limited to –COOH or –COOR4 (C1–C6 esters) and A/B/D substituents are limited to H/halogen/alkyl/hydroxy/alkoxy.
• Salt and formulation coverage is explicit, and method-of-use for allergic reactions is claimed.
• Process claims (12–17) extend the estate beyond end products to synthesis routes built on substantially pure regioisomers and defined acylation/hydrolysis/coupling or halogenation intermediates.
• Design-around options are narrow if an accused API remains within the same scaffold and ester/side-chain ranges; the main technical levers are likely (1) moving outside the R3/R4 definitions, (2) using substitution patterns outside A/B/D allowed sets, and (3) avoiding steps tied to “substantially pure regioisomer” recovery in the claimed process.

FAQs

1) Does US 5,578,610 cover both carboxylic acid and ester forms?
Yes. Claim 1 limits R3 to –COOH or –COOR4, where R4 is C1–C6.

2) Are salts covered if the base compound is within claim 1?
Yes. Claim 1 explicitly covers “a salt thereof.”

3) Do the process claims require producing “substantially pure regioisomers”?
Yes. Claim 12 requires providing a substantially pure regioisomer, and dependent process claims emphasize generating regioisomer mixtures followed by recovery of substantially pure regioisomer.

4) Can competitors avoid infringement by switching formulations to add additional actives?
Claim 10 (“consists essentially of”) may narrow that dependent formulation claim, but claim 8 still covers pharmaceutical compositions comprising carrier and the claimed compound, without an “essentially of” restriction shown in the provided text.

5) What is the biggest litigation lever in this patent’s scope: chemical differences or purity/isomer arguments?
Both. Chemical mapping to claim 1’s scaffold and R-group limits is central, while infringement can also turn on whether the marketed material is “substantially pure” and/or a specific regioisomer enrichment product.

References

1. United States Patent 5,578,610. “Piperidine derivative compounds and methods.” (Claim set provided in prompt; bibliographic details not provided.)

Drugs Protected by US Patent 5,578,610

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 5,578,610

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	174589
Austria	254594
Austria	322473
Australia	1742299
Australia	5837296
Australia	670004
Australia	699799