United States Patent 5,633,272 Landscape: Scope, Claim Coverage, and Competitive Freedom-to-Operate for 4-[5-Substituted-3-phenyl-isoxazol-4-yl]benzenesulfonamide and Related Inflammation Indications
US 5,633,272 is a US patent built around a broad Markush structure covering isoxazole-linked benzenesulfonamides (and salts) with variable substituents at (i) the benzenesulfonamide side chain (R1), (ii) the isoxazole aromatic portion (R3), and (iii) a terminal substituent set (R4). The claims extend to: (1) compound claims (Formula II and Formula III), (2) a composition claim using the same compound families, and (3) method-of-use claims for “treating inflammation or an inflammation-associated disorder,” including arthritis, pain, and fever as dependent examples.
The actionable claim takeaway is that infringement risk is driven by whether a competitor’s API falls within the enumerated substituent space for the isoxazole-benzenesulfonamide scaffold and whether the competitor makes or sells for inflammatory indications that read on the method claims.
What is US Patent 5,633,272 scope: what structures do the claims cover (Formula II, III, R1/R3/R4)?
Direct answer: The patent claims families of compounds having an isoxazole core linked to a substituted benzenesulfonamide framework, parameterized by R1, R3, and R4, plus salts. It also claims a pharmaceutical composition containing those compounds and methods for treating inflammation.
How the claim architecture works
US 5,633,272 is structured as:
-
Compound claims
- Claim 1: “compound of Formula II” with:
- R1 = broad substituent set (alkyl, carboxyalkyl, alkoxycarbonyl, aminocarbonyl, amino, haloalkoxy, alkylthio variants, aralkyl/alkoxy variants, etc.)
- R3 = cycloalkyl/cycloalkenyl/aryl (optionally substituted)
- R4 = lower alkyl, hydroxyl, or amino
- plus pharmaceutically acceptable salts
- Claim 6: “compound of Formula III” with similar variable definitions but placed under a different formula identifier
- Claims 2-4, 7-8 provide narrower substituent subsets and then extend to enumerated representative compounds.
-
Pharmaceutical composition
- Claim 9/10/11/12 (and 26/27) cover compositions comprising therapeutically effective amounts of the claimed compound families, including a named representative (Claim 12) and specific listed variants.
-
Method-of-use
- Claim 14-17: treating inflammation or an inflammation-associated disorder via administering therapeutically effective amounts of the Formula II compounds.
- Claim 18-21: additional method claims tied to Formula III compounds and dependent indication examples: arthritis, pain, fever.
- Claims 19-20 are “for use” phrasing and are indication-relevant.
R1 coverage: how broad is the substituent space?
The patent uses Markush-style definition of R1. Across Claims 1-4 (Formula II) and Claims 6-8 (Formula III), R1 includes:
- Hydrogen-bonding / functional groups: hydroxyl, amino, hydroxyalkyl, carboxyl, alkylaminoalkyl, aminoalkyl
- Protected/derivative-like groups: alkoxycarbonyl, aminocarbonyl, alkoxycarbonylalkyl, alkoxycarbonylthioalkyl, alkylaminocarbonyloxyalkyl, etc.
- Lipophilic and heteroatom substituents: alkyl, cycloalkyl, aralkyl, haloalkyl, alkylthio, thioether variants
- Halogenated ethers/alkoxys: haloalkoxy
- Aralkoxy/aryloxy/arylthio linkers: aralkoxy, aryloxyalkyl, arylthioalkyl
Claims 2-3 and 7 narrow this space with “lower” limits, e.g., lower alkyl, lower carboxyalkyl, lower haloalkoxy, lower alkylsulfonyl, etc.
R3 coverage: what ring systems are permitted?
R3 is consistently defined as:
- Base set: cycloalkyl, cycloalkenyl, and aryl
- Substitution allowed: one or more radicals including alkyl, cyano, carboxyl, alkoxycarbonyl, haloalkyl, hydroxyl, hydroxyalkyl, haloalkoxy, amino, alkylamino, arylamino, nitro, alkoxyalkyl, alkylsulfinyl, alkylsulfonyl, aminosulfonyl, halo, alkoxy, alkylthio.
Claims 4 and 8 provide more concrete substituted aryl and cycloalkyl examples:
- R3 examples include phenyl, naphthyl, biphenyl; cyclohexyl/cyclopentyl/cycloheptyl; and cyclohexenyl/cyclopentenyl variants.
R4 coverage: what terminal substituent set is allowed?
R4 is limited across the independent formulas to:
- lower alkyl
- hydroxyl
- amino
This is a key gating element. If a competitor uses a different terminal substituent class (e.g., halogen not tied into the Markush lists, carboxyl not included in R4, etc.), it can fall outside the literal scope.
Representative “anchor” compound explicitly claimed
The patent includes a specific named structure repeated across compound and method/composition claims:
- Claim 5: 4-[5-methyl-3-phenyl-isoxazol-4-yl]benzenesulfonamide (and salts)
- Claim 12/17/25/26/27/28/29: same anchor compound in composition/method contexts or as part of broader enumerated groups.
This anchor provides a concrete infringement reference point for freedom-to-operate (FTO) screening.
How many claims cover compounds vs compositions vs methods in US 5,633,272?
Direct answer: The patent includes compound claims (1-8), composition claims (9-13, 26-27), and method-of-use claims (14-25, 28-29). Dependent claims enumerate specific embodiments and indications.
Claim type map
| Claim numbers |
Type |
Coverage driver |
| 1-4 |
Compound (Formula II) |
Broad Markush over R1/R3/R4 with substitution options |
| 5 |
Compound (specific embodiment) |
4-[5-methyl-3-phenyl-isoxazol-4-yl]benzenesulfonamide |
| 6-8 |
Compound (Formula III) |
Similar Markush with “Formula III” definition |
| 9-13 |
Composition |
Same compound family embedded into pharmaceutical composition claims |
| 14-17 |
Method of treating inflammation |
Administration of Formula II compounds for inflammation |
| 18-20 |
Method of treating inflammation |
Administration of Formula III compounds; dependent indications |
| 21-22-23 |
Dependent inflammation-associated disorders |
Arthritis, pain, fever |
| 24-25 |
Compound enumeration |
Lists of specific members spanning sulfonamides and related acids/derivatives |
| 26-27 |
Composition enumeration |
Selected members from Claim 24’s list |
| 28-29 |
Method enumeration |
Selected member(s) for use in treatment |
Which specific compounds are explicitly listed in the patent (Claim 24 group)?
Direct answer: Claim 24 enumerates a large set of specific members within the broader Markush family, including multiple 5-substituted-3-phenyl isoxazole-linked benzenesulfonamides, plus some sulfonic acids and other substituted side-chain variants.
What the enumerated set signals for scope
When a patent enumerates specific structures after broad Markush claims, it indicates:
- The specification and prosecution supported those specific embodiments as within the invented genus.
- Competitors using close analogs around the isoxazole-5-position and aryl substitutions have straightforward infringement mapping.
Enumerated examples (non-exhaustive, as presented in the claim)
Claim 24 includes, among others:
This breadth matters for design-around: R4 being limited to lower alkyl/hydroxyl/amino in the independent formula could still permit many variants via other positions captured by R1 and R3 substitution rules.
What patents protect: are there likely overlapping US filings beyond 5,633,272 for same scaffold (genus coverage vs process vs salts)?
Direct answer: From the claim text alone, 5,633,272 is a genus-level compound and method patent covering inflammatory use of these isoxazole-sulfonamide families. The claim structure suggests the patent is built to block multiple analogs and downstream products (API, formulations, and indication-driven prescribing).
Landscape characterization (based on claim design, not external dossier)
Within a typical patent family structure for this type of Markush set, overlapping or complementary protection commonly includes:
- Salt and polymorph claims (salts are explicitly included, but the provided excerpt does not show dedicated polymorph/salt claims)
- Synthesis/process claims (not shown in the excerpt)
- Additional genus/species claims with narrower substituent sets
- Method-of-use claims for specific inflammatory disorders (arthritis, pain, fever are explicitly listed)
Because the provided information is claim text only, the analysis cannot assert which other patents exist in the same family or which continuations exist.
How strong is the patent estate for US 5,633,272: claim breadth, attack surfaces, and infringement likelihood?
Direct answer: Strength is high on claim breadth because independent compound claims use wide Markush ranges for R1 and R3 with optional substitution, plus R4 gating. Strength is also reinforced by method-of-use claims tied to inflammation and inflammation-associated disorders (arthritis, pain, fever). The main practical attack surface is literal scope mapping for designs that change substituent classes outside the R1/R3/R4 definitions.
Breadth indicators in the claim text
- R1 includes many functional-group families and linker variants.
- R3 allows multiple aryl systems and broad optional substitution lists.
- R4 limits endpoint types to lower alkyl/hydroxyl/amino, which may be used for design-around but also may be satisfied by many medicinal chem inputs.
Key infringement mapping gates
A competitor’s API likely faces risk if it:
- Matches the isoxazole-benzenesulfonamide scaffold captured by Formula II/III; and
- Uses R4 = lower alkyl/hydroxyl/amino; and
- Uses R3 within aryl/cycloalkyl/cycloalkenyl with optional substitutions enumerated; and
- Employs an R1 substituent set that fits within the Markush categories.
Formulation and combination risk
Composition claims (9-13) do not add extra constraints beyond including a therapeutically effective amount of a claimed compound family. If a competitor’s formulation contains a covered API, composition infringement is likely.
Which regulatory and Orange Book questions matter: how would this patent affect generic entry for an NDA that references these compounds?
Direct answer: If a commercial product is approved with this exact API as the active ingredient, US 5,633,272 being listed in the FDA’s Orange Book (Drug and Therapeutic Equivalence Evaluations) would block or delay generic approval depending on patent status and whether a Paragraph IV challenge is filed against the relevant listed claims.
This analysis cannot determine Orange Book listings because the necessary product-to-patent mapping and FDA listing data are not provided.
Method-of-use vs composition-patent impact
- If Orange Book lists method-of-use claims, a Paragraph IV challenge can still be relevant if the generic seeks to reference the same indication and label.
- If Orange Book lists compound and composition claims, generic substitution is more directly constrained.
What generic entry risks exist for competitors: how to evaluate literal design-around vs non-infringing alternatives?
Direct answer: Risk is concentrated in close analogs of the anchor scaffold and close substitution patterns around the isoxazole and sulfonamide ring systems. The design-around strategy that reduces risk is to change substituents so they fall outside at least one of the R1, R3, or R4 Markush categories as defined.
Practical design-around levers
- Change the R4 endpoint from lower alkyl/hydroxyl/amino into an excluded class (as an example, an anionic/heterocyclic substituent not captured by the “lower alkyl/hydroxyl/amino” definitions).
- Use R3 ring systems not within cycloalkyl/cycloalkenyl/aryl, or employ substitutions that are not in the enumerated optional substituent set.
- Modify R1 so it is not one of the enumerated substituent classes (e.g., remove the ability to fit within the Markush list categories).
Why the enumerated set matters
Claim 24 lists many 5-alkyl and 5-aryl substituted members and multiple aryl substitution patterns, reducing the space for “close but not literally claimed” arguments if a competitor is near the listed embodiments.
Timeline: when does this patent lose exclusivity? (expiration and term signals)
Direct answer: US 5,633,272’s term and end-of-exclusivity date depend on filing and any patent term adjustments. The filing date, issue date, and PTA/terminal disclaimer facts are not included in the provided materials, so a correct expiration date cannot be stated.
What patent litigation affects 5,633,272: Paragraph IV challenges, settlements, and injunction risk?
Direct answer: The provided materials do not include litigation history, district courts, dockets, settlement dates, or Paragraph IV filings. Those are required to map enforcement risk by date and jurisdiction.
How does US 5,633,272 compare with nearby inventions: genus vs species protection and indication coverage
Direct answer: The patent is genus-forward, with broad Formula II/III Markush coverage and then species-like enumerations through dependent claims and listed member groups. It also spans:
- API coverage (compound claims)
- Product coverage (pharmaceutical compositions)
- Label/usage coverage (methods for inflammation and inflammation-associated disorders)
This makes it less vulnerable to a simple “formulation-only” workaround if the API is still in-scope, and it makes it more likely to affect generic labeling and prescribing for the inflammation indications if method-of-use claims are asserted.
Key Takeaways
- US 5,633,272 claims broad isoxazole-linked benzenesulfonamide families via Formula II/III Markush definitions using R1, R3, and R4, plus salts.
- The patent covers compound claims, a pharmaceutical composition claim, and method-of-use claims for inflammation and inflammation-associated disorders, with explicit dependent examples: arthritis, pain, fever.
- The anchor compound is explicitly claimed: 4-[5-methyl-3-phenyl-isoxazol-4-yl]benzenesulfonamide.
- Dependent and enumeration claims (especially Claim 24) list many specific analogs, tightening infringement risk around close structural variants.
- Practical FTO screening should focus on whether a candidate API and its substituents fit within the enumerated R1/R3/R4 categories and whether the product is marketed/used for the inflammatory indications captured by the method claims.
FAQs
1) Does US 5,633,272 cover only 4-[5-methyl-3-phenyl-isoxazol-4-yl]benzenesulfonamide?
No. Claim 5 is a specific embodiment, but independent claims 1 and 6 cover broader Formula II/III compound families with extensive R1/R3/R4 substituent options, and Claim 24 enumerates additional members.
2) Are pharmaceutical compositions claimed even if the API is within the genus?
Yes. Claims 9-13 and 26-27 include pharmaceutical composition claims containing therapeutically effective amounts of the covered compound families.
3) Does the patent include method-of-use protection for specific inflammatory indications?
Yes. Claims 14-17 cover inflammation treatment broadly, and Claims 21-23 provide examples of inflammation-associated disorders including arthritis, pain, and fever.
4) What substitution positions are most likely to determine literal infringement?
The Markush definitions for R1, R3, and the terminal set R4 are determinative for literal scope. R4 is limited to lower alkyl, hydroxyl, or amino.
5) Can a generic avoid infringement by changing formulation only?
If the API itself falls within the claimed Formula II/III families, composition claims can still be implicated. Avoiding infringement generally requires designing the API outside at least one R1/R3/R4 constraint, or limiting labeling/indication exposure if method-of-use claims are asserted in a label-driven theory.
References (APA)
No external sources were cited because the prompt provided only US 5,633,272 claim text and did not include filing/issue dates, specification details beyond the excerpt, prosecution history, FDA/Orange Book listings, or litigation records.
