US Patent 4,567,264: Scope, Claims, and U.S. Patent Landscape
What does US 4,567,264 actually claim?
US Drug Patent 4,567,264 claims a narrow set of piperazine-based carbamoylmethyl derivatives defined by a general scaffold with tightly bounded substituent patterns. The independent claim set is directed to (i) the free base compound in a specific structural genus and (ii) pharmaceutically acceptable esters and acid-addition salts of those compounds.
The user-provided claim language identifies three specific embodiments (claim 1, claim 2, claim 3), each corresponding to a defined substitution pattern on:
- a 3-(substituted phenoxy)-2-hydroxypropyl side chain, and
- a 4-(aminocarbonylmethyl) piperazine core bearing a 2,6-dimethylphenyl (claim 1 and 3) or the analogous ring-substituted variant pattern (claim 2).
All three claims are written to cover the exact substitution patterns plus salts/esters. There is no allegation in the provided claim text of broad Markush expansion beyond the enumerated R-group constraints.
How are the claimed compounds scoped (claims 1 to 3)?
Below is the scope as expressed by the R-group constraints and the corresponding named embodiments given in the claims.
Claim 1 scope
Claim 1 covers the compound and its pharmaceutically acceptable esters and acid-addition salts where:
- R1 and R5 are each methyl
- R2, R3, R4 are each hydrogen
- R6 to R12 are each hydrogen
Named embodiment (as stated in the claim):
- 1-[3-phenoxy-2-hydroxypropyl]-4-[2,6-dimethylphenyl)aminocarbonylmethyl]-piperazine
- plus pharmaceutically acceptable esters and acid addition salts
Claim 2 scope
Claim 2 covers the compound and its pharmaceutically acceptable esters and acid-addition salts where:
- R1 and R5 are each methyl
- R2, R3, R4 are each hydrogen
- R6 is methoxy
- R7 to R12 are each hydrogen
Named embodiment (as stated in the claim):
- 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-[(2,6-dimethylphenyl)-aminocarbonylmethyl]-piperazine
- plus pharmaceutically acceptable esters and acid addition salts
Claim 3 scope
Claim 3 covers the compound and its pharmaceutically acceptable esters and acid-addition salts where:
- R1 and R5 are each methyl
- R2, R3, R4 are each hydrogen
- R6 is cyano
- R7 to R12 are each hydrogen
Named embodiment (as stated in the claim):
- 1-[3-(2-cyanophenoxy)-2-hydroxypropyl]-4-[2,6-dimethylphenyl)aminocarbonylmethyl]piperazine
- plus pharmaceutically acceptable esters and acid addition salts
Scope summary table
| Claim |
Substituent on phenoxy ring (as constrained by R6) |
Other phenoxy substituents (R7-R12) |
Core substitution (R1, R5) |
Other R-groups (R2-R4) |
Covered salts/esters |
| 1 |
H (phenoxy unsubstituted) |
H |
methyl |
H |
Yes |
| 2 |
methoxy (2-methoxyphenoxy) |
H |
methyl |
H |
Yes |
| 3 |
cyano (2-cyanophenoxy) |
H |
methyl |
H |
Yes |
What is the practical claim coverage: genus vs. enumeration?
The provided claims read like a small, substitution-controlled genus with three claim-embodiments that differ only by the substituent at R6 on the phenoxy ring:
- R6 = hydrogen (Claim 1)
- R6 = methoxy (Claim 2)
- R6 = cyano (Claim 3)
Everything else is fixed by the R-group constraints in each claim:
- R1 and R5 always methyl
- R2-R4 always hydrogen
- R7-R12 always hydrogen
- the 2,6-dimethylphenyl appears fixed in the named embodiments
So the “scope” is not a large Markush universe; it is controlled by multiple binding constraints and, based on the enumerated embodiments provided, the commercially relevant differentiation is likely limited to the phenoxy substituent at the position corresponding to R6.
How do esters and acid-addition salts expand enforceability?
Each independent claim explicitly includes:
- pharmaceutically acceptable esters, and
- pharmaceutically acceptable acid addition salts
This expands coverage beyond the free base by capturing common formulation variants used in drug development. Practically, that means a generic applicant cannot avoid infringement merely by switching from a free base to a salt or an appropriate ester, as long as the salt/ester is “pharmaceutically acceptable” and falls within the claim scope.
However, the expansion is derivative: it attaches to the same underlying structural compound defined by the claim’s R-group constraints.
Claim construction implications for design-arounds
Based on the explicit R-group constraints stated in the claims, design-around strategy must change at least one constraint that is positively required, such as:
- Alter R6 away from hydrogen/methoxy/cyano in the corresponding claim.
- Alter R1 or R5 away from methyl (if those positions are truly required by the structure formula and defined in the claim).
- Alter R2-R4 away from hydrogen.
- Alter any of R7-R12 away from hydrogen.
Because the claims are tightly constrained, many “nearby” analogs (different phenoxy substitution at a different position, different substitution on the phenoxy ring, or changes in the piperazine-linked substituent pattern) can fall outside the scope if they violate a constraint.
What is the likely U.S. patent landscape structure around this claim set?
With only the claim text provided and without the patent record (title, assignee, filing/priority dates, related applications, prosecution history, or family members), the only defensible “landscape” analysis is structural: how this patent would sit relative to typical U.S. drug IP layers.
In general, U.S. coverage around a claim like this typically breaks into four layers:
- Compound patent(s): claims to the free base and pharmaceutically acceptable salts/esters, like US 4,567,264.
- Formulation patents: claims to salt forms, dosage units, dissolution/pH profiles, or manufacturing processes.
- Method-of-use patents: claims to treatment of a disease with the compound.
- Manufacturing/process patents: claims to synthetic routes or intermediates.
Given the claim language you supplied is compound-specific, US 4,567,264 functions as the compound layer. That usually means:
- it blocks marketing of the exact claimed compounds and claimed salts/esters,
- it does not, by itself, block non-compound variants such as formulations or methods unless those methods are also claimed elsewhere in the portfolio.
What would matter most for freedom-to-operate (FTO) in the U.S.?
For an FTO screen of US 4,567,264’s compound claims, the key is not just the scaffold but the specific substitution constraints. The practical FTO questions that flow directly from the claim text are:
- Does the candidate drug substance match one of these three phenoxy substituent states at the position mapped to R6?
- If yes, is the formulation presented as a free base, an ester, or an acid-addition salt that is “pharmaceutically acceptable” and would still be considered within the claim language?
- If no, does it still violate the fixed requirements on R1/R5 being methyl and R2-R4 being hydrogen (and R7-R12 being hydrogen)?
Because the claim text tightly fixes multiple sites, a candidate that changes only one element (for example, altering the phenoxy substitution position or substituting the phenoxy ring at a different site) can evade coverage if it breaks a defined R constraint.
How strong is the enforceability position of these claims?
Strength indicators derived from claim language (not from external evidence):
- The claims are direct compound claims, which are generally enforceable against generics that make and sell the same active ingredient.
- The salts/esters language reduces common avoidance routes used in generic development.
- The enumerated substitution patterns are narrow, which can limit reach against close analogs.
Overall, the enforceability is strong against exactly these compounds and their accepted salt/ester derivatives, and weaker against analogs that change a fixed substituent constraint.
Key takeaways
- US 4,567,264 claims specific piperazine-carbamoylmethyl derivatives with fixed R-group constraints and expressly covers pharmaceutically acceptable esters and acid-addition salts.
- The compound coverage as provided is effectively split across three phenoxy substitution states at the position mapped to R6: H (Claim 1), methoxy (Claim 2), cyano (Claim 3).
- Because the claims constrain many positions to methyl or hydrogen, design-arounds likely require changing at least one of the positively required R-group assignments, not just making a minor change in formulation.
- For a U.S. landscape view, this patent sits in the compound layer, with typical portfolio spillover into formulation/method/process only if separately claimed in related patents (not provided in the claim text you supplied).
FAQs
-
Does US 4,567,264 cover only the free base?
No. Each claim also covers pharmaceutically acceptable esters and acid addition salts of the claimed compounds.
-
What differentiates claim 1 from claim 2 and claim 3?
The claimed difference is the substituent corresponding to R6 on the phenoxy ring: hydrogen (claim 1), methoxy (claim 2), and cyano (claim 3), with all other specified R-groups remaining fixed by the claim.
-
Can a generic avoid infringement by switching to a different salt form?
Not if the salt is a pharmaceutically acceptable acid addition salt of the claimed compound, because the claims expressly include those salts.
-
Is the patent a broad Markush genus over many analogs?
Based on the provided claim R-group constraints and the explicit named embodiments, it functions as a narrow, substitution-controlled set rather than a wide open-ended genus.
-
What is the most likely portfolio role of this patent in the U.S.?
It is a compound-layer asset that blocks marketing of the exact claimed active ingredient(s) and their claimed salt/ester derivatives; other layers (formulation/method/process) would typically be covered only by separate patents if present.
References
[1] User-provided claim text for United States Drug Patent 4,567,264 (claims 1 to 3).
