Details for Patent: 5,002,953

United States Patent 5,002,953 scope and claims analysis: formula (I) heteroaryl thiazolidinedione compounds, salts/solvates, compositions, and hyperglycaemia/hyperlipidaemia methods

US Patent 5,002,953 claims a broad chemical genus of thiazolidinedione (TZD) derivatives framed by a Markush formula (I) and sub-genus definitions around substituted heteroaryl groups (A1) and a substituted benzene motif (A2), with explicit coverage of tautomeric forms, pharmaceutically acceptable salts, and pharmaceutically acceptable solvates. The independent claim also includes enumerated exemplars that lock in a set of specific benzothiazolyl, benzoxazolyl, oxazolyl, thiazolyl, pyridyl, and pyrimidinyl substituents. The patent further adds downstream protection for pharmaceutical compositions (claim 52) and therapeutic methods (claims 53 to 55) for hyperglycaemia and hyperlipidaemia, including combination treatment wording (claim 55).

Claim architecture at a glance

• Independent chemical claim: claim 1, “compound of formula (I)” plus tautomer/salt/solvate language.
• Chemical sub-claims: claims 2 to 51 narrow A1 and/or specific moiety embodiments (formula (a) to (e) fragments; specific A1 classes).
• Enumerated compounds: claims 12 to 51 list specific end-point structures, mainly variants of the same TZD core with different heteroaryl substituents on an anilide-like sidechain.
• Formulation: claim 52 pharmaceutical composition using any compound of formula (I).
• Methods of use: claims 53 to 55 for hyperglycaemia and hyperlipidaemia, including “treatment and/or prophylaxis.”

What does the Markush formula (I) cover in US 5,002,953?

Featured snippet answer: Claim 1 covers thiazolidinedione derivatives having a defined TZD core substituted by a benzyl (benzene) ring (A2) and a sidechain terminating in a heteroaryl group (A1), with variable R1 on the TZD nitrogen-substituted position, and variable ring atom count and substitution patterns on the heteroaryl (A1). It also covers tautomeric forms, pharmaceutically acceptable salts, and pharmaceutically acceptable solvates.

Core structural constraints: A1, R1, A2, and n

Claim 1 defines the compound genus through four key variable sets:

A1: substituted/unsubstituted aromatic heterocycle (4 to 7 atoms; up to 4 hetero atoms)

• Size: “single ring aromatic heterocyclyl group having 4 to 7 ring atoms”
• Hetero atoms: “comprising up to 4 hetero atoms… selected from oxygen, sulphur or nitrogen”
• Substituents on A1: “up to 4 substituents”
  • allowed substituents: C1-12 alkyl, C1-12 alkoxy, aryl, halogen
  • adjacent-carbon aryl formation: “any two substituents on adjcent carbon atoms, together with the carbon atoms to which they are attached, may form an aryl group,” and that aryl carbon atoms may be substituted or unsubstituted.

Practical scope effect: A1 is intentionally tolerant across many benzofused/nonfused heteroaryl-like motifs, though claim 1 restricts A1 to a “single ring aromatic heterocyclyl group.” Dependent claim 2 expands to “single or fused ring” under similar constraints, which broadens the realized chemical territory.

R1: hydrogen or a defined range of substituents on the TZD/sidechain position

R1 can be:

• H
• C1-12 alkyl
• C1-6 alkylcarbonyl
• aryl-C1-12 alkyl (aryl moiety substituted/unsubstituted)
• or substituted/unsubstituted aryl group (aryl limited to phenyl/naphthyl with up to five additional substituents from a defined set)

Practical scope effect: This supports multiple N-alkyl and acyl variants and aryl-substituted variants, without needing separate Markush statements per chemical class. It also increases infringement risk for later “same core, different N-substituent” molecules.

A2: benzene ring with three optional substituents

• A2 is “a benzene ring having three optional substituents”
• those substituents can be halogen or defined alkyl/alkoxy options
• substituents set includes:
  • halogen
  • C1-12 alkyl
  • C1-12 alkoxy
  • halo-C1-12 alkyl
  • hydroxy, amino, nitro, carboxy
  • alkoxycarbonyl variants
  • alkylcarbonyloxy
  • alkylcarbonyl
  • and substituted variants are allowed by the way the substituent categories are written

Practical scope effect: This is a medium-to-broad benzene substitution window and is compatible with typical medicinal chemistry patterns for TZDs (solubility and binding tuning).

n: 2 to 6 linker/segment length (as written in the formula)

Claim 1 says n is an integer “from 2 to 6.”

Practical scope effect: n drives geometric and distance constraints in the heteroaryl-bearing sidechain. This is a key design-around axis: many competitors vary linker length; this claim blocks 2–6.

How do dependent claims narrow A1 and the heteroaryl sub-genus?

Featured snippet answer: Dependent claims 2 to 11 and 49 to 51 carve out specific A1 classes, including “single or fused ring” heterocycles and specific fragments (formula (a) to (e)), and they also set numeric restrictions like n = 2 or 3 and R1 = methyl.

Claim 2: expands A1 beyond “single ring”

Claim 2: A1 is “substituted or unsubstituted, single or fused ring aromatic heterocyclyl” with up to 4 hetero atoms.

Scope effect: If claim 1 were read narrowly to a single ring, claim 2 supplies coverage for fused-ring aromatic heterocycles, which aligns with the later enumerated compounds (e.g., benzothiazole, benzoxazole).

Claims 3 to 7: A1 moieties defined as fragments (a) to (e)

• Claim 3 introduces A1 as a moiety of formula (a), (b), or (c), with:

  • R4 and R5 each H, alkyl, or aryl, and aryl definitions with optional substitution
  • in moiety (a), X is oxygen or sulphur

• Claims 4 to 7 then specify R4/R5 patterns:

  • Claim 4: R4 and R5 are H, alkyl, or phenyl
  • Claim 5: R4 and R5 together define moiety (d) with R6/R7 as H/halogen/alkyl/alkoxy
  • Claim 6: R6 and R7 both H
  • Claim 7: A1 via moiety (e) with R8/R9 each independently H/halogen/alkyl/alkoxy
  • Claim 8: R8 and R9 both H

Scope effect: These fragments correspond to common heteroaryl scaffolds:

• benzothiazole/benzoxazole-like patterns (benzofused with adjacent heteroatoms)
• thiazole/oxazole-like motifs (smaller ring with heteroatom pair)
• pyridyl/pyrimidinyl patterns (later addressed via claims 50 and 51)

Claims 9 and 10: formula (II) and linker restriction

• Claim 9: compound of formula (II) defined by A1/R1/R2/R3/n plus R8/R9 via formula (e).
• Claim 10: n is 2 or 3.

Scope effect: If a competitor uses n = 4–6, claim 10 does not help but claim 1 does. If a competitor uses n = 2 or 3, claim 10 layers additional narrowing coverage.

Claim 11: R1 = methyl

Claim 11 locks one specific R1 end state. This is a narrowing claim that can help establish a closer read for specific asserted molecules.

Claims 49 to 51: ring-size and heteroaryl class calls

• Claim 49: A1 has 5 or 6 ring atoms
• Claim 50: A1 is substituted/unsubstituted thiazolyl, oxazolyl, pyridyl or pyrimidinyl
• Claim 51: A1 is substituted/unsubstituted oxazolyl, pyridyl or pyrimidinyl

Scope effect: These claims align strongly with the enumerated exemplars (thiazolyl/oxazolyl/pyridyl/pyrimidinyl).

What specific compounds are explicitly enumerated in the claims?

Featured snippet answer: The patent includes a long list of specific TZD derivatives in claims 12 to 48, each built on the same 2,4-thiazolidinedione core and a substituted benzyl/benzylidene sidechain that links to heteroaryl amines (benzothiazolyl, benzoxazolyl, thiazolyl, oxazolyl, pyridyl, pyrimidinyl), with the N-methyl and sometimes N-acetyl variations captured.

Common motif across enumerated compounds

The enumerated examples repeatedly use:

• 2,4-thiazolidinedione core (TZD)
• “5-(4-[…]benzyl)-2,4-thiazolidinedione” or “benzylidene” forms
• a sidechain containing N-methyl-N-(heteroarylyl)amino (and variants like N-isopropyl or N-acetyl)
• heteroaryl units from the set:
  • 2-benzothiazolyl
  • 2-benzoxazolyl
  • thiazolyl (including 4,5-dimethylthiazolyl; 4-phenylthiazolyl; methyl-substituted thiazolyl)
  • oxazolyl (including 5-phenyloxazolyl; 4,5-dimethyloxazolyl)
  • pyridyl
  • pyrimidinyl

Representative enumerated endpoints (verbatim-level structural classes)

• Benzothiazolyl amine variants:

  • claim 13: 5-(4-[2-(N-methyl-N-(2-benzothiazolyl)amino)ethoxy]benzyl)-2,4-thiazolidinedione
  • claim 14: corresponding benzylidene variant
  • further claims list multiple benzothiazolyl substituent classes (including methyl/phenyl substituted benzothiazole in the list)

• Benzoxazolyl amine variants:

  • claim 15 and 16: 2-benzoxazolyl analogs (benzyl and benzylidene)
  • claim 17 and 18: pyrimidinyl analogs
  • claim 23 and 24: 4-phenylthiazolyl analogs (benzyl and benzylidene)

• Thiazolyl/oxazolyl series:

  • claims 19 to 22: 4,5-dimethylthiazolyl and thiazolyl
  • claims 31 to 34: 5-phenyloxazolyl and 4,5-dimethyloxazolyl
  • claims 33 and 34: 4,5-dimethyloxazolyl

• Pyridyl and pyrimidinyl series:

  • claims 35 to 36: 2-pyrimidinylamino ethoxy/benzylidene
  • claims 42 and 43: 2-pyridylamino ethoxy/benzylidene

• N-substitution variants:

  • claim 37 includes N-acetyl with 2-pyrimidinylamino
  • claim 48 includes N-isopropyl with 2-benzoxazolyl

Scope effect: Enumerated examples reduce ambiguity. Even if a later adjudicator narrowed the Markush interpretation, these dependent claims identify specific target compounds within the family.

What is the scope of pharmaceutical composition protection in claim 52?

Featured snippet answer: Claim 52 covers pharmaceutical compositions comprising a non-toxic effective amount of any claim 1 compound (or tautomer/salt/solvate), plus a pharmaceutically acceptable carrier.

Composition claim elements

• active: compound of formula (I) (or tautomer/salt/solvate)
• dose language: “non-toxic effective amount”
• vehicle: “pharmaceutically acceptable carrier”

Scope effect: Standard composition coverage. The real leverage is the breadth of the chemical genus and the captured heteroaryl and substitution patterns, which means any formulation using any member of the claim 1 family can potentially fall within claim 52, absent a carve-out for particular formulations.

What therapeutic methods are claimed, and what disease coverage exists?

Featured snippet answer: Claims 53 to 55 cover methods for treatment and/or prophylaxis of hyperglycaemia and hyperlipidaemia in humans or non-human mammals, by administering an effective non-toxic amount of a compound of formula (I).

Claim-by-claim method scope

• Claim 53 (hyperglycaemia): treatment and/or prophylaxis of hyperglycaemia
• Claim 54 (hyperlipidaemia): treatment of hyperlipidaemia
• Claim 55 (combined listing): treatment and/or prophylaxis of diseases selected from hyperglycaemia and hyperlipidaemia

Administration and audience

• route is not specified
• subject: “human or non-human mammal”
• administration: “administering… effective, non-toxic amount”

Scope effect: The “selected from” disease list in claim 55 can capture either disease within the defined two-item set. It does not extend beyond those listed indications.

How broad is the patent’s compound genus versus typical TZD competitor space?

Featured snippet answer: Claim 1 is broad on substitution patterns (A1: heteroaryl with up to four hetero atoms and up to four substituents; A2: benzene with three substituents; R1: wide functional substitution set) but is structurally constrained by the TZD core, the benzyl/benzylidene arrangement in the formula drawings, the defined A1 class size (4–7 ring atoms in claim 1), and the linker/parameter n (2–6).

Design-around pressure points (in-scope vs out-of-scope)

The highest-friction boundaries for competitors are:

• n = 2–6: changing the segment length may fall outside claim 1
• A1 ring size and hetero atom limits: A1 is capped by “4 to 7 ring atoms” and “up to 4 hetero atoms,” and claim 49 narrows to 5–6
• permitted substituents on A1 and A2: if a competitor uses substitution patterns outside the defined sets (e.g., different heteroatoms or non-listed groups), literal coverage can weaken
• A1 must be aromatic heterocyclyl: non-aromatic heterocycles may avoid claim 1 unless they still read as aromatic within the patent’s definitions
• claim 2’s “fused ring” expansion: fused heteroaryls that match claim 2 are pulled back into coverage

What patent landscape issues matter if US 5,002,953 is asserted?

Featured snippet answer: US 5,002,953 is a composition and method-of-use coupled to a broad chemical genus. For litigation leverage, the core issues typically center on claim construction of Markush parameters (A1 and allowed substituents), whether accused compounds fall within those parameters, and whether downstream compositions and methods match the therapeutic claims (hyperglycaemia and hyperlipidaemia).

How the claim set maps to infringement proof

• Chemical infringement:

  • compare accused compound’s A1 heteroatom content, ring size, aromaticity, and substitution count to claim 1 limitations
  • compare A2 benzene substituents to claim 1’s allowed categories
  • confirm n range and R1 identity
  • confirm TZD core and the required benzyl/benzylidene linkage pattern from the formula (I) drawing context

• Composition infringement (claim 52):

  • accused product includes a non-toxic effective amount of a covered compound plus a pharmaceutically acceptable carrier
  • typical generics/combination products will be analyzed for whether they contain a literal genus member

• Method infringement (claims 53 to 55):

  • evaluate the indication: hyperglycaemia and hyperlipidaemia are explicitly listed
  • evaluate whether “treatment and/or prophylaxis” or treatment for hyperlipidaemia is practiced

Weakness vectors (litigation posture mechanics)

The claim set’s breadth also creates vulnerabilities that challengers typically target:

• Markush interpretation disputes: whether a competitor’s heteroaryl substituent structure “fits” the listed substituent categories
• numeric parameter mismatches: n outside 2–6; A1 ring atoms outside 4–7 (claim 1) or outside 5–6 (claim 49)
• ring-type disputes: “single ring aromatic heterocyclyl” vs fused rings (claim 2 provides some coverage but claim construction still matters)

Is this patent likely to overlap with later TZD derivatives and generic entry?

Featured snippet answer: Because claim 1 covers a large family of heteroaryl-substituted TZD compounds with flexible A1 and A2 substitution patterns and includes compositions and method-of-use claims, it is a plausible overlap candidate with later TZD analogs in the same therapeutic area, especially those using heteroaryl amine sidechains and benzyl/benzylidene substitutions.

Overlap patterns that tend to trigger risk

• substitutions on the heteroaryl ring within the allowed A1 categories (thiazole/oxazole/pyridyl/pyrimidinyl/benzofused analogs)
• N-substituent variations at the amino group consistent with R1 allowances
• formulation commercialization under the same indications (hyperglycaemia/hyperlipidaemia)

Key Takeaways

• US 5,002,953’s chemical core is a broad TZD genus controlled by Markush parameters for A1 (aromatic heterocycle size and heteroatom content), A2 (benzene tri-substitution), R1 (H/alkyl/aryl/acyl-type categories), and n = 2–6.
• Dependent claims broaden realized coverage via fused-ring allowance (claim 2) and specific heteroaryl class definitions (claims 49–51).
• The enumerated claims (12–48) lock in concrete embodiments centered on 2,4-thiazolidinedione linked to benzyl or benzylidene motifs and heteroaryl amines (benzothiazolyl, benzoxazolyl, thiazolyl, oxazolyl, pyridyl, pyrimidinyl), including N-methyl and select N-substituent variants.
• Downstream protection extends to compositions and therapeutic methods: claim 52 covers formulations with pharmaceutically acceptable carriers; claims 53–55 cover treatment and/or prophylaxis for hyperglycaemia and hyperlipidaemia in humans and non-human mammals.

FAQs

1) Which parts of claim 1 are most important for claim construction in chemical infringement?
The A1 definition (ring atom count, heteroatoms, aromaticity, substitution limits), R1 substitution categories, A2 benzene tri-substitution scope, and n range (2–6) are the highest-sensitivity constraints.

2) Does the patent cover both benzyl and benzylidene TZD variants?
Yes. The enumerated compounds explicitly include both “benzyl” and “benzylidene” 2,4-thiazolidinedione embodiments, consistent with claim 1’s formula family.

3) Can competitors rely on changing linker length to avoid the patent?
Potentially. Claim 1 restricts n to 2–6, with additional dependent narrowing to n = 2 or 3 in claim 10.

4) Are fused heteroaryl rings covered?
Yes. Claim 1 speaks to “single ring aromatic heterocyclyl,” but claim 2 expressly expands A1 to “single or fused ring aromatic heterocyclyl.”

5) What indications are covered for methods of use?
Hyperglycaemia and hyperlipidaemia are covered. Claim 53 targets hyperglycaemia, claim 54 targets hyperlipidaemia, and claim 55 covers treatment and/or prophylaxis for diseases selected from those two.

References

No external sources were cited because the request provided only the claim text and not bibliographic details, prosecution history, patent publication metadata, or related filings.