|
Patent landscape, scope, and claims: |
United States Patent 5,583,141 (Claim Scope, Coverage Boundaries, and US Patent Estate Impact for Angiotensin II Antagonists)
US Drug Patent 5,583,141 claims a broad genus of substituted heterocycle carboxylic-acid (and derivatives) compounds plus pharmaceutical composition and method-of-use coverage for “antagonizing angiotensin II.” Claim 1 is the primary driver: it is written as a Markush-style chemical genus with layered substituent definitions (R1, R2, R3, and a defined benzimidazole/thienoimidazole/imidazopyridine-like core) and includes explicit exclusion of one benzimidazole-7-carboxylic-acid species. Downstream dependent claims narrow to specific R2 heterocycles (oxadiazole/thiadiazole), specific core classes (benzimidazole, imidazopyridine), and specific exemplified final compounds. The estate’s real-world scope is governed by the breadth-to-enabling ratio in Claim 1 and the remaining validity risks for genus claims if prior art exists against the heterocycle-carboxylate architecture and angiotensin II antagonism.
Key structural anchor in Claim 1
- Core scaffold: group “selected from” benzimidazole, thienoimidazole, or imidazopyridine (and additional structure selections later in dependent claims).
- Linker/aryl fragment: recurring “biphenyl-4-yl methyl” type motif appears in the dependent exemplars and in the excluded compound’s name.
- Heterocycle R2: explicitly includes 2,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl and 2,5-dihydro-5-oxo-1,2,4-thiadiazol-3-yl (and related oxadiazole/thiadiazole/thioxo variants).
- Carboxylate/acid handling via R3: claim language covers optionally esterified or amidated carboxyl, with multiple acid-derivative and protecting-group options, and explicitly includes non-carboxyl acid salts (tetrazolyl, trifluoromethanesulfonic amide, phosphoric acid, sulfonic acid).
- Exclusion: “excluding the compound 2-ethoxy-1-[[2’-(2,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl]benzimidazole-7-carboxylic acid and its physiologically acceptable salts.”
What patents protect angiotensin II antagonists covered by US 5,583,141?
Featured-snippet answer: US 5,583,141 protects a chemical genus (Claim 1) of substituted benzimidazole/thienoimidazole/imidazopyridine angiotensin II antagonists with an R2 1,2,4-oxadiazole or thiadiazole-like substituent and a carboxyl or carboxyl-derivative group, plus pharmaceutical compositions and methods of use to antagonize angiotensin II (Claims 31–32).
Claim 1 coverage logic (genus claim): what is actually inside the fence
Claim 1 is framed as: “A compound or a salt thereof” with layered Markush substituents:
- R1: “optionally substituted hydrocarbon residue … optionally bound through a hetero-atom.”
- Dependent claims further restrict R1 to lower alkyl/alkenyl/alkynyl/cycloalkyl, aryl/aralkyl, and specific bound-hetero-atom variants (N(R9), O, S(O)m).
- R2: a defined heterocycle group with i = –O– or –S– and j = >C=0 or >C=S.
- Dependent claims specify R2 as 2,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl (Claim 16) and the corresponding thiadiazole variant (Claims 17–18).
- R3: “optionally esterified or amidated carboxyl, tetrazolyl, trifluoromethanesulfonic amide, phosphoric acid or sulfonic acid,” including protection with lower alkyl or acyl.
- Defined group structure selection (Claim 1, plus dependent claims 6 and 21): core selection between benzimidazole, thienoimidazole, or imidazopyridine; later claims specify structural variants (Claims 19–22).
- Explicit exclusion: the single species “2-ethoxy-…benzimidazole-7-carboxylic acid” (and salts) is excluded from the genus.
Coverage implication: a competitor compound is likely to infringe Claim 1 if it matches the same core class + the same R2 heterocycle family + carboxyl/derivative handling options, regardless of many R1 substitutions. Non-matching R2 or core class is the primary design-around lever.
What else is protected beyond the chemical genus
- Claim 31: pharmaceutical composition for antagonizing angiotensin II containing a compound of Claim 1 (or salt) plus standard carriers/excipients.
- Claim 32: method-of-use for antagonizing angiotensin II via administering a therapeutically effective amount of a Claim 1 compound (or salt).
What is the detailed scope of Claim 1 for US 5,583,141 (R1/R2/R3 and core constraints)?
Featured-snippet answer: Claim 1 defines a Markush genus built on a benzimidazole/thienoimidazole/imidazopyridine core bearing a biphenyl-methyl substituted arrangement with an R2 2,5-dihydro-5-oxo-1,2,4-oxadiazole or related heterocycle, and a carboxyl group that may be converted to esters/amides or represented as various acid/salt forms, while permitting a wide range of R1 substituents and heteroatom linkages.
R1 scope: breadth and the practical boundary created by heteroatom binding
Claim 1: R1 is an optionally substituted hydrocarbon residue, bound through a heteroatom when applicable.
Dependent claims tighten R1 in multiple ways:
- Claim 2: R1 is lower (C2-4) alkyl bound through –O–, –NH– or –S–.
- Claims 12–15 and 13/14/15: R1 can be alkyl/alkenyl/alkynyl/cycloalkyl (Claim 12), aryl/aralkyl (Claim 13), lower (C1-8) alkyl or (C2-8) alkenyl (Claim 14), or narrower alkyl/alkenyl bands (Claim 15).
- Heteroatom linker options in R1:
- –N(R9)– where R9 = hydrogen or lower (C1-4) alkyl (Claims 12–13)
- –O–
- –S(O)m– where m = 0–2 (Claims 12–15)
- Substitution tolerance on R1 includes hydroxy, amino, halogen, lower alkoxy, and lower alkylthio (Claim 12 and others).
Design-around observation: if a candidate changes the linker type from N/O/S(O)m alternatives, or uses a substantially different substituent topology outside “optionally substituted hydrocarbon residue” bounds, it may fall outside Claim 1.
R2 scope: the key chemical discriminator
Claim 1 defines R2 generically via:
- i = –O– or –S–
- j = >C=0 or >C=S
Dependent claims convert that generic to specific ring members:
- Claim 16: R2 is 2,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl
- Claim 17: R2 is 2,5-dihydro-5-oxo-1,2,4-thiadiazol-3-yl
- Claim 18: R2 is 2,5-dihydro-5-thioxo-1,2,4-oxadiazol-3-yl
Design-around lever: compounds with different heterocycle chemistry (not matching the oxadiazole/thiadiazole family defined by i and j, or not tautomeric equivalents) are the cleanest path out of Claim 1.
R3 scope: carboxyl handling and salt/derivative inclusion
Claim 1: R3 may be
- optionally esterified or amidated carboxyl
- tetrazolyl
- trifluoromethanesulfonic amide
- phosphoric acid or sulfonic acid
- protected with optionally substituted lower alkyl or acyl
Dependent claims specify:
- Claim 3 and 10: R3 includes specific groups:
- --CO--D where D is hydroxy/amino/N-alkylamino/alkoxy (with substitution tolerance) or
- --O--CH(R4)--OCOR5 (a dioxolane/dioxolenyl-type protecting/derivative representation with R4 and R5 definitions).
- Claim 4: tighter D variants including hydroxy, amino, N-alkylamino, N,N-di-lower alkylamino, lower alkoxy with possible substitution, or tetrazolyl optionally protected.
- Claim 5: carboxyl optionally esterified.
- Claim 8–11 and 9: R3 options include amidated/esterified carboxyl, plus “--CO--D” structures with defined D sets; Claim 11 allows R3 = carboxyl (i.e., acid form).
Design-around lever: if a follow-on program uses a fundamentally different terminal acid surrogate not encompassed by the R3 definitions, it could reduce Claim 1 risk. If it uses ester salts/derivatives that still meet R3 definitions, it remains within scope.
Core class scope
- Claim 6: “group … is benzimidazole, thienoimidazole or imidazopyridine structure.”
- Claim 19: “group … is benzimidazole or imidazopyridine.”
- Claims 21–22: the group has structure selected from listed substructures (Claim 21) and R2 in Claim 22 is again restricted to oxadiazole vs thiadiazole.
Which specific compounds are exemplified or explicitly called out in US 5,583,141 dependent claims?
Featured-snippet answer: Dependent claims 24–30 list specific final compounds that map onto the Claim 1 scaffold with particular R1 and R2 substitutions, all within the angiotensin II antagonist genus, while Claim 1 itself excludes one specific benzimidazole-7-carboxylic acid species.
Explicit exclusions
- Claim 1 exclusion:
“2-ethoxy-1-[[2’-(2,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl]benzimidazole-7-carboxylic acid and its physiologically acceptable salts.”
Exemplified/named compounds in dependent claims
- Claim 24: 1-(cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1-[[2’-(2,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl]benzimidazole-7-carboxylate
- Claim 25: 1-[2’-(2,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl-4-methyl-2-propoxythieno[3,4-d]imidazole-6-carboxylic acid
- Claim 26: 2-ethyl-1-[[2’-(2,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl]benzimidazole-7-carboxylic acid
- Claim 27: 2-ethoxy-1-[[2’-(2,5-dihydro-5-oxo-1,2,4-thiadiazol-3-yl)biphenyl-4-yl]methyl]benzimidazole-7-carboxylic acid
- Claim 28: 2-ethyl-3-[[2’-(2,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl]-5,7-dimethylimidazo[4.5-b]pyridine
- Claim 29: 1-[[2’-(2,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl]2-methoxy-4-methylthieno[3,4-d]imidazole-6-carboxylic acid
- Claim 30: 2-cyclopropyl-1-[[2’-(2,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl]benzimidazole-7-carboxylic acid
Litigation-relevant point: the excluded compound is a benzimidazole-7-carboxylic acid with an ethoxy substituent and an oxadiazole R2. That creates a targeted carve-out within a broader benzimidazole family coverage.
How does the angiotensin II method-of-use coverage work in Claim 32, and what does it require?
Featured-snippet answer: Claim 32 is a standard use claim: it covers administering a therapeutically effective amount of a Claim 1 compound (or salt) to a mammal for the purpose of antagonizing angiotensin II.
Claim 32 elements
- Administering to a mammal
- A therapeutically effective amount
- Of a Claim 1 compound or salt
- For the purpose of antagonizing angiotensin II
Risk profile
- If a product contains a Claim 1-structure compound, Claim 32 creates direct infringement exposure for on-label use.
- If the compound matches Claim 1 but marketing labels or compendia usage differ, dispute becomes claim interpretation and evidence of intended/used antagonism.
What formulation and prodrug boundaries are implied by R3 (esters/amides/salt forms)?
Featured-snippet answer: R3 explicitly includes esterified and amidated carboxyl groups and multiple acid/sulfonate/phosphoryl and protected variants, which broadens claim coverage to prodrugs and salt forms that still fall within the R3 Markush language.
Practical coverage buckets inside R3
- Acid form: R3 = carboxyl (Claim 11)
- Ester/prodrug-like: “optionally esterified or amidated carboxyl” (Claim 1) plus specific “--O--CH(R4)--OCOR5” type derivative representations (Claims 3 and 10)
- Amide and tetrazolyl: includes tetrazolyl, trifluoromethanesulfonic amide, phosphoric acid, sulfonic acid (Claim 1) and additional D variants in dependent claims
Formulation design-around note (mechanistic): changing to a terminal group not expressed by the R3 Markush sets (not a covered ester, amide, or listed acid/salt form) reduces exposure. Switching between covered ester and acid forms does not avoid infringement if the prodrug converts in vivo to the claimed terminal acid and the claim reaches the administered species.
When does US 5,583,141 lose exclusivity, and what could still extend protection?
Featured-snippet answer: No expiration/exclusivity date can be computed from the claim text alone. The timing of loss of exclusivity depends on application/filing date, issuance date, any patent term adjustment, and whether any patent term extension applies. The provided text does not include those inputs.
What generic entry risks exist for products whose API matches the Claim 1 genus?
Featured-snippet answer: Entry risk is highest when a generic ANDA or 505(b)(2) product uses an API that satisfies Claim 1’s R1/R2/core/capability for R3 (acid or covered derivative), and it is marketed for angiotensin II antagonism. Risk decreases when the API changes the R2 heterocycle family or the terminal group outside R3.
Generic scenario map
- Scenario A (high risk): API contains the claimed core class + R2 = oxadiazole/thiadiazole family + R3 = carboxylic acid/covered ester/amidated derivative.
- Likely exposure: Claim 1 (product), Claim 31 (composition), Claim 32 (method-of-use).
- Scenario B (medium risk): API deviates in R1 but still matches R2/core/R3.
- Likely remains within Claim 1 due to broad R1 Markush definition.
- Scenario C (lower risk): API uses a non-matching heterocycle R2 or a non-listed core class, or uses a terminal group outside R3’s definition.
- Likely outside Claim 1. Dependent claims also tend to follow from Claim 1, so the whole chain narrows.
How strong is the patent estate for this scaffold based on claim architecture alone?
Featured-snippet answer: The estate strength is driven by Claim 1’s genus coverage and its multi-layer Markush flexibility around R1 and R3. The single explicit exclusion and the dependent claim narrowing to specific R2 heterocycles and core substructures create both (1) breadth and (2) interpretive boundaries that could be litigated on claim construction and prior-art enablement.
Strength signals inside the claim language
- Broad Markush on R1 and multiple heteroatom linkers (N(R9), O, S(O)m) supports coverage of many analogs.
- R3 coverage captures not only acids but also ester and amidated prodrug-like derivatives and salt/acid derivatives.
- Core definition includes multiple fused ring systems: benzimidazole, thienoimidazole, imidazopyridine.
- Method-of-use claims broaden enforcement beyond product infringement.
Potential weakness signals inside the claim language
- The genus is broad while the excluded compound suggests at least one species lies outside desired claim scope, which can correlate with prior-art overlap issues (handled through explicit exclusion).
- The enforceable reach depends on how courts construe “optionally substituted hydrocarbon residue,” the meaning of “bound through a hetero-atom,” and the exact mapping of the “group of the formula” constructs.
Key Takeaways
- US 5,583,141 Claim 1 is a broad genus claim centered on benzimidazole/thienoimidazole/imidazopyridine angiotensin II antagonists with an R2 oxadiazole/thiadiazole family heterocycle and a carboxyl terminal that can be an acid, ester, amide, or covered acid/salt derivative.
- Claims 31–32 extend protection to pharmaceutical compositions and therapeutic administration to antagonize angiotensin II.
- The primary chemical design-around paths are (1) changing the R2 heterocycle family away from the oxadiazole/thiadiazole family defined by i/j, and/or (2) moving the terminal functionality outside R3’s covered acid/ester/amidated/salt/protected sets, while (3) R1 edits alone are less likely to avoid Claim 1 due to breadth.
- One benzimidazole-7-carboxylic-acid species is explicitly excluded from the genus, which narrows the fence for that specific ethoxy/oxadiazole structure.
FAQs
-
Does US 5,583,141 cover prodrugs that convert to the claimed carboxylic acid in vivo?
Yes where the administered prodrug structure still matches Claim 1’s R3 ester/amidated/protected derivative definitions.
-
What part of the molecule is the most important for infringement of Claim 1?
The combination of (i) the core class (benzimidazole/thienoimidazole/imidazopyridine) and (ii) the R2 oxadiazole/thiadiazole-family heterocycle, plus (iii) an R3 terminal group within the carboxyl/ester/amidated/salt/protected language.
-
Can altering R1 avoid infringement while keeping R2 and the core the same?
Often not, because R1 is defined broadly in Claim 1 and is further expanded in dependent claims.
-
Are pharmaceutical compositions and treatment methods separately protected?
Yes. Claim 31 covers compositions and Claim 32 covers methods of antagonizing angiotensin II.
-
How does the explicit exclusion in Claim 1 affect coverage of close analogs?
It carves out the specifically named benzimidazole-7-carboxylic acid species with the stated ethoxy and oxadiazole R2, while leaving the rest of the genus potentially intact for analogs that differ in the excluded structural elements.
References
- US Patent 5,583,141. (Claim text provided in prompt).
More… ↓
⤷ Start Trial
|
