Scope and Claims of US Patent 4,024,271 and the US Patent Landscape for H2-Histamine Receptor Inhibition (incl. Formulation and Gastric Acid Secretion Coverage)
Executive summary: US 4,024,271 covers methods and compositions for inhibiting H2 histamine receptors and gastric acid secretion using a defined heterocyclic guanidine chemical class (including a specific imidazole-containing example), with additional limitations tied to the heterocycle substitution pattern (A, X1, X2, k, m, Y, E, R1, R2) and exclusions (notably the proviso restricting a specific X1 substituent to cases where E is NH or N-cyano). The claim set includes (i) method-of-treatment claims (H2 inhibition and gastric acid secretion), (ii) dependent claims locking to a specific compound (N-cyano-N'-methyl-N"-[2-((4-methyl-5-imidazolyl)-methylthio)ethyl]guanidine) and (iii) pharmaceutical composition claims with oral dosage forms and dose ranges. From a freedom-to-operate standpoint, the patent’s scope is defined primarily by the guanidine core and the enumerated substitution framework rather than by a broad “any H2 blocker” approach, which narrows design-around opportunities to chemistries that fall outside the described formula or outside the proviso constraints.
What is US Patent 4,024,271 claiming for H2 histamine receptor inhibition?
What do independent claims cover?
US 4,024,271 contains two parallel independent method claims (one framed as H2 receptor inhibition and one framed as gastric acid secretion inhibition), plus composition claims that track the same active-ingredient formula.
Claim 1 (method):
A method of inhibiting H-2 histamine receptors by administering an effective amount of a heterocyclic compound of the formula recited in the claim.
Claim 6 (method):
A method of inhibiting gastric acid secretion by administering an effective amount of the same heterocyclic compound formula framework.
What chemical framework limits the claims?
Both method claims require a heterocyclic compound defined by a multi-parameter formula:
- Heterocycle identity (A): imidazole, pyrazole, pyrimidine, pyrazine, or pyridazine ring, formed together with the carbon atom shown to generate an unsaturated heterocyclic nucleus.
- Substitution variables:
- X1 can be hydrogen, lower alkyl, hydroxyl, trifluoromethyl, benzyl, halogen, amino, or another substituent drawn in the claim (where E' is NH or N-cyano).
- X2 is hydrogen or (under certain X1 conditions) lower alkyl or halogen.
- k is 0 to 2 and m is 2 or 3, with the constraint k + m = 3 or 4.
- Heteroatom substitution (Y): oxygen, sulphur, or NH.
- Amine/guanidine substituent block (E, R1, R2):
- E is NR2
- R1 is hydrogen, lower alkyl, or di-lower alkylamino-lower alkyl
- R2 is hydrogen, nitro, or cyano
- Salt coverage: “or a pharmaceutically acceptable addition salt thereof.”
- Proviso limiting a specific X1 substituent:
X1 is [the specific depicted substituent] only when E is NH or N-cyano.
This proviso matters for scope because it ties the allowed substitution pattern at X1 to the identity of E. Claims like these often collapse design-around strategies because substituents that look “equivalent” may be excluded by the proviso if they do not meet the linked condition.
What is the practical claim trigger?
Infringement requires that the administered (or formulated) compound:
- falls within the recited formula variable set, including the k + m constraint, and
- satisfies the proviso linkage between X1 and E, and
- is administered in an effective amount for H2 inhibition (Claim 1) or gastric acid secretion inhibition (Claim 6).
Because the claims are “method” claims, use evidence typically turns on the therapeutic indication and the compound’s pharmacologic effect consistent with the claim framing.
Which specific compound in US 4,024,271 is singled out in the dependent claims?
Dependent claim 2 and 7 lock to a named example
The patent’s dependent claims narrow the broad formula to a specific heterocyclic guanidine:
Claim 2 (method):
The heterocyclic compound is:
- N-cyano-N'-methyl-N"-[2-((4-methyl-5-imidazolyl)-methylthio)ethyl]guanidine
or a pharmaceutically acceptable addition salt.
Claim 7 (method):
Same locked compound limitation for the gastric acid secretion method.
Free base limitation appears in dependent claims 3 and 8
- Claim 3: the locked compound is in the free base form.
- Claim 8: same free base limitation for the gastric acid secretion method.
This creates separate infringement lanes: a salt could still fall under Claim 2/7, but the free base is expressly covered under Claim 3/8.
What dosing, route, and composition limitations are added in US 4,024,271?
Route and dose range limitations
For the specific compound (Claims 3–5 for H2 inhibition):
- Claim 4: administered orally.
- Claim 5: daily dosage regimen from about 150 mg to about 1000 mg.
These limitations narrow the scope to oral administration and that daily range for the specific compound (free base form under Claim 3).
Composition claim coverage
Claim 9 (composition):
A pharmaceutical composition to inhibit H2 receptors comprising:
- pharmaceutical carrier, and
- an effective amount of the same heterocyclic compound formula.
Claims 10–13 narrow the composition further:
- Claim 10: locked compound (with salt option).
- Claim 11: locked compound in free base form.
- Claim 12: composition is in the form of a tablet or capsule.
- Claim 13: locked compound amount about 50 mg to about 250 mg (for the composition).
How these composition limits interact with method claims
A composition infringement theory does not always require proving the claimed method effect (depending on jurisdiction and how “to inhibit” is treated). Still, practically, the same compound identity drives both composition and method claim coverage.
What is the scope of the formula variables (A, X1, X2, k, m, Y, E, R1, R2) in claim construction terms?
Heterocycle A defines the pharmacophore “family”
Because A is limited to five ring types (imidazole, pyrazole, pyrimidine, pyrazine, pyridazine), the claims do not read on arbitrary heteroaryl substituents outside those ring classes.
X1 and X2 control positional substitution
X1 offers broader variability (H, lower alkyl, OH, CF3, benzyl, halogen, amino, plus one additional depicted substituent class tied to E'). X2 is restricted to H or (under conditional X1 conditions) lower alkyl or halogen.
k and m impose a numeric substitution constraint
The parameters k (0 to 2) and m (2 or 3) with k + m = 3 or 4 narrow the possible substitution count on the heterocycle scaffold. This is a concrete constraint that can be checked against a candidate structure.
Y restricts link position heteroatoms
Y is oxygen, sulphur, or NH, which limits the heteroatom type at the relevant position in the scaffold.
E, R1, and R2 determine the guanidine substitution pattern
- E is NR2
- R1 can be H, lower alkyl, or di-lower alkylamino-lower alkyl
- R2 is H, nitro, or cyano
This cluster is central: it defines the guanidine substitution and thus often serves as the main design-around lever.
The proviso is a scope gating condition
The claim expressly limits when X1 can take a particular depicted substituent: it can only occur when E is NH or N-cyano. That means an otherwise plausible substitution pattern may still be excluded if E does not match.
How does US 4,024,271 compare to a “generic H2 blocker” claim strategy?
US 4,024,271 is formula-driven, not class-by-activity
The patent does not claim “inhibiting H2 receptors” in the abstract. The method claims are tethered to a defined heterocyclic compound formula with tightly constrained variables. That is materially different from later-era patents that often claim:
- broader “compound class” formulae with wider ranges, or
- claims keyed to specific pharmacological parameters rather than substitution constraints.
Two parallel use theories, same active-ingredient scaffold
- H2 receptor inhibition (Claim 1)
- gastric acid secretion inhibition (Claim 6)
These are often asserted together against the same product since both arise from H2 receptor antagonism, but in prosecution and litigation, the act-of-use framing can matter for claim interpretation.
What patents protect the same territory in the United States? (Landscape map approach)
The request is to analyze the “scope and claims and patent landscape” for US 4,024,271, but the provided content includes only the claims text and no bibliographic identifiers beyond the patent number. A complete and accurate landscape requires jurisdictional capture of:
- related continuations/divisionals,
- corresponding foreign family members,
- later blocking patents on salts, specific crystalline forms, dosing regimens, or combination therapy,
- Orange Book listings (if any) and FDA labels.
Without those bibliographic and linking inputs, a reliable landscape cannot be produced here in a way that is complete or accurate.
Accordingly, only the internal claim architecture of US 4,024,271 can be analyzed from the information provided.
Key Takeaways
- US 4,024,271 is a formula-limited patent for H2 histamine receptor inhibition and gastric acid secretion inhibition.
- Independent method claims (1 and 6) require administering an effective amount of a heterocyclic compound defined by specific variable constraints (A ring class, X1/X2 substitutions, k + m = 3 or 4, Y atom type, E/R1/R2 pattern) plus a proviso linkage restricting a specific X1 substituent to cases where E is NH or N-cyano.
- Dependent claims narrow to a specific compound: N-cyano-N'-methyl-N"-[2-((4-methyl-5-imidazolyl)-methylthio)ethyl]guanidine, including both salt and free base forms.
- Additional limitations are layered onto that specific compound for oral administration (Claim 4), a 150 mg to 1000 mg daily regimen (Claim 5), and tablet/capsule formulation with 50 mg to 250 mg per unit amount (Claims 12–13).
FAQs
-
Does US 4,024,271 cover both free base and salt forms?
Yes. Dependent claims cover salts (Claims 2 and 7) and separately cover the free base (Claims 3 and 8, plus Claims 11 and 12–13 for compositions).
-
Is oral administration required to infringe under the narrower claims?
Yes for the specific compound under Claim 4; broader formula method claims can still cover non-oral administration if the formulation and structure fall within Claims 1/6 scope (subject to use proof).
-
What is the role of the proviso that ties X1 to E?
It restricts when the depicted substituent at X1 is allowed, only permitting it when E is NH or N-cyano, narrowing permissible structures within the claimed formula.
-
What are the key numeric constraints on the heterocycle substitution pattern?
k is 0 to 2, m is 2 or 3, with the requirement that k + m equals 3 or 4, limiting the substitution count.
-
Do the composition claims require a tablet or capsule?
Not all composition claims. Claim 9 is broad to “pharmaceutical composition,” while Claim 12 specifically narrows to tablets or capsules and Claim 13 narrows the per-dose amount range.
References (APA)
- US Patent 4,024,271.
