United States Patent 4,376,858 (4,376,858) Scope, Claims, and U.S. Patent Landscape for Quinazoline Isethionate and Glucuronate Salts

United States Patent 4,376,858 claims specific quinazoline free-base species and two salt forms defined by Z as either 2-hydroxyethanesulfonic acid (isethionic acid) or glucuronic acid. Claim scope is driven by (i) a formula limitation on the core quinazoline substitution pattern and (ii) salt identity (Z). Independent coverage centers on the salt compounds; dependent claims narrow to particular named salts and to specific solid-state forms (crystalline vs powdery).

What does US Patent 4,376,858 claim: scope of formula coverage for Z = isethionate vs glucuronate?

Core chemical claim boundary

Claim 1 defines “a compound of the formula” with a structural quinazoline scaffold and a specified substitution pattern (as represented by the formula in the patent). The only explicit variable definition provided in your excerpt is Z, where:

Z is 2-hydroxyethanesulfonic acid (2-hydroxyethanesulfonate) or
Z is glucuronic acid (glucuronate)

This structure-to-salt linkage means claim 1 coverage is a salt-based subset of quinazoline derivatives. It does not, by the excerpt, appear to cover:

other counterions beyond those two,
free base forms without Z, or
alternative crystal forms unless they map to claims 4 and 5.

Claim 1 is a “species by salt identity” claim

Practically, this is a typical salt-specification claim: enforceability and infringement hinge on whether the accused compound is the same quinazoline cation paired with the asserted anion (isethionate or glucuronate), regardless of manufacturing route.

What the claim does not say (based on provided claim text)

Based only on the claim excerpt, claim 1 does not expressly include:

salts with mixed counterions,
hydrates/solvates unless tied to “crystalline form” (claim 4) or “powdery form” (claim 5),
alternative substitution patterns on the quinazoline ring beyond those shown in the formula.

Which exact compounds are covered by dependent claims in US 4,376,858?

Claim 2: named isethionate salt

Claim 2 narrows claim 1 to the specific salt name:

2,4-diamino-5-methyl-6-[(3,4,5-trimethoxyanilino)methyl]quinazoline monoisethionate

Key scope effect:

“monoisethionate” indicates one isethionate per base molecule (1:1 salt stoichiometry). In infringement, counterion stoichiometry can matter if an accused product is a different salt ratio or has different ionization state.

Claim 3: named glucuronate salt

Claim 3 narrows claim 1 to the specific salt name:

2,4-diamino-5-methyl-6-[(3,4,5-trimethoxyanilino)methyl]quinazoline glucuronate

Here the salt is defined as “glucuronate,” again implying a specific pairing of the quinazoline base with glucuronic acid-derived anion.

Relationship of claims 2 and 3 to claim 1

Claims 2 and 3 function as exemplified embodiments of claim 1’s formula + Z language. Enforceability often tracks these narrower embodiments when proof of precise salt identity is easier than proving formula mapping for a broader set.

What solid-state forms are protected: crystalline vs powdery claims in US 4,376,858?

Claim 4: crystalline form of the monoisethionate

Claim 4 states:

The compound of claim 2 being in crystalline form

This creates a second layer of protection tied to morphology/solid-state form. If an accused manufacturer sells a non-crystalline (amorphous) form, claim 4 may not be met even if the chemical salt identity is correct.

Claim 5: powdery form of the glucuronate

Claim 5 states:

The compound of claim 3 being in powdery form

This similarly ties coverage to physical form. “Powdery form” is less stringent than “crystalline” in terms of precision, but it still creates an additional element that must be present in an accused product.

Key enforcement implication

For litigation, claim 4 and claim 5 tend to require analytical characterization linking the commercial product to the claimed solid-state description (e.g., solid-state characterization supporting crystallinity vs amorphous/powder morphology).

How does the claim structure map to infringement: what must an accused product show to fall within scope?

Chemical identity test (claims 1-3)

To infringe claims 1-3, an accused product must contain:

the specified quinazoline cation with the substitution pattern shown in the formula; and
the specified anion:
- isethionate (claim 1 or claim 2), or
- glucuronate (claim 1 or claim 3).

If either the quinazoline core substitution pattern differs or the anion differs from Z, the claim elements are not satisfied.

Solid-state test (claims 4-5)

To infringe claims 4-5, the accused product must also satisfy:

crystalline form for the monoisethionate (claim 4), and/or
powdery form for the glucuronate (claim 5).

What is the likely patent landscape around US 4,376,858: salts, hydrates/solvates, and polymorph risk?

Adjacent protective themes that commonly cluster with salt claims

Even without additional claim text from the rest of the family, a salt-and-solid-state patent typically sits within a landscape that includes:

the same quinazoline free base and alternative salts (different counterions),
polymorphs (different crystal lattices),
hydrates/solvates (forms incorporating water or solvents),
process claims (methods of forming the salt, crystallization control).

Given that 4,376,858 explicitly claims only two anions (isethionate and glucuronate) and only one solid-state characterization per anion (crystalline for claim 4, powdery for claim 5), the commercial knock-on risks typically come from:

competing salt forms that are not covered by Z,
alternative solid-state forms that are not “crystalline” or not “powdery,”
new patents targeting specific polymorphs or manufacturing controls for these salts.

Competitive landscape within salt space

If a generic or competitor uses:

the same quinazoline core and uses isethionate or glucuronate, chemical identity can trigger overlap with claim 1 and its dependent species.
a different counterion (e.g., other organic acids or inorganic salts), it can design around the anion limitation.
the same salt but a different solid-state form, it can design around claims 4 and 5.

When does US 4,376,858 lose exclusivity: patent expiration mechanics for a 1983-era filing?

Patent term baseline

For a utility patent filed in the early 1980s (4,376,858 is in the 1983 issue era), the baseline expiration generally tracks 17 years from issuance under the then-applicable regime, subject to possible adjustments or term adjustments that depend on the specific prosecution timeline.

Key practical point for business

Because the patent number and issue era predate modern patent term adjustment frameworks for most cases, the likely practical outcome is that the patent is long expired in the U.S. This typically means any current enforcement would be limited to:

refiled/family members with later priority,
reissued patents,
or other overlapping patents not addressed by 4,376,858 alone.

(Your prompt asks for scope and landscape; the claims you provided do not contain issuance/filing dates, so term calculation cannot be stated precisely from the excerpt alone.)

What generic entry risks exist for salt-based claims like these in the U.S.?

Salt switching as a design-around

The Z limitation creates a clean design-around path:

if a generic uses the same quinazoline free base but selects a different counterion, claims keyed to isethionate/glucuronate should not be met.

Solid-state switching as another design-around

Even if the same anion is used:

crystalline vs powdery differences can reduce the probability of meeting claims 4 and 5.

But note the risk from claim 1

Even if solid-state is engineered to avoid claim 4 or 5, claim 1 still captures the compound by formula and Z identity. So a design around based only on solid-state may not suffice if an accused product remains a claimed salt species.

How strong is the patent estate for this compound: likely claim strength drivers

Strength drivers

Chemical specificity: The salt identity is explicitly defined for two anions, and dependent claims specify named salts.
Clear element boundaries: Claims 2-3 define monoisethionate and glucuronate by name, which typically supports clear claim construction.

Strength limiters

Narrow counterion set: Only two anions are claimed.
Solid-state narrowing: claims 4-5 add morphology elements that are often contested and require analytical proof.

Typical litigation posture

For salt claims, disputes typically center on:

whether the accused product is truly the claimed salt (analytical confirmation of counterion/stoichiometry),
whether crystalline/powder description is met,
whether the product is a different form (polymorph, hydrate, solvate, amorphous).

How do these claims compare with typical quinazoline salt patents: what is the differentiator?

This patent’s differentiator

This patent’s independent coverage is framed around:

a defined quinazoline substitution pattern and
two specific anions (isethionate and glucuronate) with follow-on solid-state dependent claims.

Compared with patents that claim broad “salts with acids” or “pharmaceutically acceptable salts” in genus form, 4,376,858 is narrower on counterions but potentially easier to enforce when the defendant uses the claimed anion and marketed material is characterized as crystalline/powdery as recited.

Key Takeaways

Claim 1 covers a defined quinazoline cation paired with Z = 2-hydroxyethanesulfonate (isethionate) or Z = glucuronate.
Claim 2 narrows to 2,4-diamino-5-methyl-6-[(3,4,5-trimethoxyanilino)methyl]quinazoline monoisethionate.
Claim 3 narrows to 2,4-diamino-5-methyl-6-[(3,4,5-trimethoxyanilino)methyl]quinazoline glucuronate.
Claim 4 adds a solid-state limitation: crystalline monoisethionate.
Claim 5 adds a solid-state limitation: powdery glucuronate.
The commercial design-around is primarily anion switching; a secondary design-around is solid-state/form switching to avoid claim 4/5 while recognizing claim 1 still targets the salt species.

FAQs

Can a different quinazoline substitution pattern avoid infringement of US 4,376,858?
Yes, because claims 1-3 are limited by the formula depiction of the specific quinazoline substitution pattern.
Does using isethionate instead of glucuronate avoid all claims?
No. Using isethionate maps to Z and can still infringe claim 1 and claim 2, with claim 4 depending on crystallinity.
If a product uses the correct anion but is amorphous, does it avoid claim 4 or claim 5?
It may avoid the morphology-dependent dependent claims (claim 4 or 5), but claim 1 can still be implicated if the anion and core structure match.
Are hydrates or solvates covered by claim 4/5?
Not on the face of the provided excerpt. The excerpt ties coverage to “crystalline form” and “powdery form,” not specifically to hydrate or solvate descriptors.
What is the main patent landscape risk for a competitor targeting these salts?
Overlap is most likely where competitors also use the same isethionate/glucuronate anions and market products in the claimed solid forms.

References

United States Patent No. 4,376,858. Claims text as provided in prompt (Z = 2-hydroxyethanesulfonic acid or glucuronic acid; dependent named salt compounds; claim 4 crystalline form; claim 5 powdery form).

Title:	2-4-Diamino-5-methyl-6-[(3,4,5-trimethoxyanilino)methyl]quinazoline salts
Abstract:	2,4-Diamino-5-methyl-6-[(3,4,5-trimethoxyanilino)methyl]quinazoline salts, pharmaceutical compositions containing said salts, methods of treating malaria, and bacterial infections employing said salts and compositions and methods for producing said salts.
Inventor(s):	Norman L. Colbry
Assignee:	Warner Lambert Co LLC
Application Number:	US06/344,350
Patent Claim Types: see list of patent claims	Compound;
Patent landscape, scope, and claims:	United States Patent 4,376,858 (4,376,858) Scope, Claims, and U.S. Patent Landscape for Quinazoline Isethionate and Glucuronate Salts United States Patent 4,376,858 claims specific quinazoline free-base species and two salt forms defined by Z as either 2-hydroxyethanesulfonic acid (isethionic acid) or glucuronic acid. Claim scope is driven by (i) a formula limitation on the core quinazoline substitution pattern and (ii) salt identity (Z). Independent coverage centers on the salt compounds; dependent claims narrow to particular named salts and to specific solid-state forms (crystalline vs powdery). What does US Patent 4,376,858 claim: scope of formula coverage for Z = isethionate vs glucuronate? Core chemical claim boundary Claim 1 defines “a compound of the formula” with a structural quinazoline scaffold and a specified substitution pattern (as represented by the formula in the patent). The only explicit variable definition provided in your excerpt is Z, where: Z is 2-hydroxyethanesulfonic acid (2-hydroxyethanesulfonate) or Z is glucuronic acid (glucuronate) This structure-to-salt linkage means claim 1 coverage is a salt-based subset of quinazoline derivatives. It does not, by the excerpt, appear to cover: other counterions beyond those two, free base forms without Z, or alternative crystal forms unless they map to claims 4 and 5. Claim 1 is a “species by salt identity” claim Practically, this is a typical salt-specification claim: enforceability and infringement hinge on whether the accused compound is the same quinazoline cation paired with the asserted anion (isethionate or glucuronate), regardless of manufacturing route. What the claim does not say (based on provided claim text) Based only on the claim excerpt, claim 1 does not expressly include: salts with mixed counterions, hydrates/solvates unless tied to “crystalline form” (claim 4) or “powdery form” (claim 5), alternative substitution patterns on the quinazoline ring beyond those shown in the formula. Which exact compounds are covered by dependent claims in US 4,376,858? Claim 2: named isethionate salt Claim 2 narrows claim 1 to the specific salt name: 2,4-diamino-5-methyl-6-[(3,4,5-trimethoxyanilino)methyl]quinazoline monoisethionate Key scope effect: “monoisethionate” indicates one isethionate per base molecule (1:1 salt stoichiometry). In infringement, counterion stoichiometry can matter if an accused product is a different salt ratio or has different ionization state. Claim 3: named glucuronate salt Claim 3 narrows claim 1 to the specific salt name: 2,4-diamino-5-methyl-6-[(3,4,5-trimethoxyanilino)methyl]quinazoline glucuronate Here the salt is defined as “glucuronate,” again implying a specific pairing of the quinazoline base with glucuronic acid-derived anion. Relationship of claims 2 and 3 to claim 1 Claims 2 and 3 function as exemplified embodiments of claim 1’s formula + Z language. Enforceability often tracks these narrower embodiments when proof of precise salt identity is easier than proving formula mapping for a broader set. What solid-state forms are protected: crystalline vs powdery claims in US 4,376,858? Claim 4: crystalline form of the monoisethionate Claim 4 states: The compound of claim 2 being in crystalline form This creates a second layer of protection tied to morphology/solid-state form. If an accused manufacturer sells a non-crystalline (amorphous) form, claim 4 may not be met even if the chemical salt identity is correct. Claim 5: powdery form of the glucuronate Claim 5 states: The compound of claim 3 being in powdery form This similarly ties coverage to physical form. “Powdery form” is less stringent than “crystalline” in terms of precision, but it still creates an additional element that must be present in an accused product. Key enforcement implication For litigation, claim 4 and claim 5 tend to require analytical characterization linking the commercial product to the claimed solid-state description (e.g., solid-state characterization supporting crystallinity vs amorphous/powder morphology). How does the claim structure map to infringement: what must an accused product show to fall within scope? Chemical identity test (claims 1-3) To infringe claims 1-3, an accused product must contain: the specified quinazoline cation with the substitution pattern shown in the formula; and the specified anion: isethionate (claim 1 or claim 2), or glucuronate (claim 1 or claim 3). If either the quinazoline core substitution pattern differs or the anion differs from Z, the claim elements are not satisfied. Solid-state test (claims 4-5) To infringe claims 4-5, the accused product must also satisfy: crystalline form for the monoisethionate (claim 4), and/or powdery form for the glucuronate (claim 5). What is the likely patent landscape around US 4,376,858: salts, hydrates/solvates, and polymorph risk? Adjacent protective themes that commonly cluster with salt claims Even without additional claim text from the rest of the family, a salt-and-solid-state patent typically sits within a landscape that includes: the same quinazoline free base and alternative salts (different counterions), polymorphs (different crystal lattices), hydrates/solvates (forms incorporating water or solvents), process claims (methods of forming the salt, crystallization control). Given that 4,376,858 explicitly claims only two anions (isethionate and glucuronate) and only one solid-state characterization per anion (crystalline for claim 4, powdery for claim 5), the commercial knock-on risks typically come from: competing salt forms that are not covered by Z, alternative solid-state forms that are not “crystalline” or not “powdery,” new patents targeting specific polymorphs or manufacturing controls for these salts. Competitive landscape within salt space If a generic or competitor uses: the same quinazoline core and uses isethionate or glucuronate, chemical identity can trigger overlap with claim 1 and its dependent species. a different counterion (e.g., other organic acids or inorganic salts), it can design around the anion limitation. the same salt but a different solid-state form, it can design around claims 4 and 5. When does US 4,376,858 lose exclusivity: patent expiration mechanics for a 1983-era filing? Patent term baseline For a utility patent filed in the early 1980s (4,376,858 is in the 1983 issue era), the baseline expiration generally tracks 17 years from issuance under the then-applicable regime, subject to possible adjustments or term adjustments that depend on the specific prosecution timeline. Key practical point for business Because the patent number and issue era predate modern patent term adjustment frameworks for most cases, the likely practical outcome is that the patent is long expired in the U.S. This typically means any current enforcement would be limited to: refiled/family members with later priority, reissued patents, or other overlapping patents not addressed by 4,376,858 alone. (Your prompt asks for scope and landscape; the claims you provided do not contain issuance/filing dates, so term calculation cannot be stated precisely from the excerpt alone.) What generic entry risks exist for salt-based claims like these in the U.S.? Salt switching as a design-around The Z limitation creates a clean design-around path: if a generic uses the same quinazoline free base but selects a different counterion, claims keyed to isethionate/glucuronate should not be met. Solid-state switching as another design-around Even if the same anion is used: crystalline vs powdery differences can reduce the probability of meeting claims 4 and 5. But note the risk from claim 1 Even if solid-state is engineered to avoid claim 4 or 5, claim 1 still captures the compound by formula and Z identity. So a design around based only on solid-state may not suffice if an accused product remains a claimed salt species. How strong is the patent estate for this compound: likely claim strength drivers Strength drivers Chemical specificity: The salt identity is explicitly defined for two anions, and dependent claims specify named salts. Clear element boundaries: Claims 2-3 define monoisethionate and glucuronate by name, which typically supports clear claim construction. Strength limiters Narrow counterion set: Only two anions are claimed. Solid-state narrowing: claims 4-5 add morphology elements that are often contested and require analytical proof. Typical litigation posture For salt claims, disputes typically center on: whether the accused product is truly the claimed salt (analytical confirmation of counterion/stoichiometry), whether crystalline/powder description is met, whether the product is a different form (polymorph, hydrate, solvate, amorphous). How do these claims compare with typical quinazoline salt patents: what is the differentiator? This patent’s differentiator This patent’s independent coverage is framed around: a defined quinazoline substitution pattern and two specific anions (isethionate and glucuronate) with follow-on solid-state dependent claims. Compared with patents that claim broad “salts with acids” or “pharmaceutically acceptable salts” in genus form, 4,376,858 is narrower on counterions but potentially easier to enforce when the defendant uses the claimed anion and marketed material is characterized as crystalline/powdery as recited. Key Takeaways Claim 1 covers a defined quinazoline cation paired with Z = 2-hydroxyethanesulfonate (isethionate) or Z = glucuronate. Claim 2 narrows to 2,4-diamino-5-methyl-6-[(3,4,5-trimethoxyanilino)methyl]quinazoline monoisethionate. Claim 3 narrows to 2,4-diamino-5-methyl-6-[(3,4,5-trimethoxyanilino)methyl]quinazoline glucuronate. Claim 4 adds a solid-state limitation: crystalline monoisethionate. Claim 5 adds a solid-state limitation: powdery glucuronate. The commercial design-around is primarily anion switching; a secondary design-around is solid-state/form switching to avoid claim 4/5 while recognizing claim 1 still targets the salt species. FAQs Can a different quinazoline substitution pattern avoid infringement of US 4,376,858? Yes, because claims 1-3 are limited by the formula depiction of the specific quinazoline substitution pattern. Does using isethionate instead of glucuronate avoid all claims? No. Using isethionate maps to Z and can still infringe claim 1 and claim 2, with claim 4 depending on crystallinity. If a product uses the correct anion but is amorphous, does it avoid claim 4 or claim 5? It may avoid the morphology-dependent dependent claims (claim 4 or 5), but claim 1 can still be implicated if the anion and core structure match. Are hydrates or solvates covered by claim 4/5? Not on the face of the provided excerpt. The excerpt ties coverage to “crystalline form” and “powdery form,” not specifically to hydrate or solvate descriptors. What is the main patent landscape risk for a competitor targeting these salts? Overlap is most likely where competitors also use the same isethionate/glucuronate anions and market products in the claimed solid forms. References United States Patent No. 4,376,858. Claims text as provided in prompt (Z = 2-hydroxyethanesulfonic acid or glucuronic acid; dependent named salt compounds; claim 4 crystalline form; claim 5 powdery form). More… ↓ ⤷ Start Trial

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Details for Patent: 4,376,858

Summary for Patent: 4,376,858