US Patent 4,962,115: Scope, Claim Set, and Landscape

US Patent 4,962,115 is built around a cis-disubstituted piperidine benzamide scaffold with extensive substituent latitude at three phenyl-position variables (R3/R4/R5) and a variable “L” linker that can include aryl ether/alkyl ether segments, with coverage extended to salts, stereoisomers, quaternary ammonium salts, and downstream GI motility product and method claims.

What is the core claimed chemical scope?

1) Claim 1 is the backbone: a Markush compound formula plus stereochemistry and attachment constraints

Claim 1 recites a compound defined by (i) a specific piperidine ring substitution pattern and cis configuration at positions 3 and 4, (ii) defined variability at R1, R2, R3, R4, R5, and (iii) a defined variability at L with multiple structural sub-classes.

Key structural scope elements in Claim 1:

Stereochemical constraint: “the substituents in the 3 and 4 positions in the piperidine ring have the cis configuration”
Salt coverage:
- “pharmaceutically acceptable acid addition salts”
- “stereochemically isomeric forms”
- “pharmaceutically acceptable quaternary ammonium salts”
Substituent variables:
- R1: H, lower alkyl, (Ar1) lower alkyl, lower alkylcarbonyl, aminolower alkyl, mono- and di(lower alkyl)aminolower alkyl
- R2: H or lower alkyl
- R3, R4, R5: independently H, lower alkyl, lower alkyloxy, halo, hydroxy, cyano, nitro, amino, mono- or di(lower alkyl)amino, aminocarbonyl, (Ar1)carbonylamino, lower alkylcarbonylamino, lower alkylcarbonyl, lower alkylcarbonyloxy, aminosulfonyl, lower alkylsulfinyl, lower alkylsulfonyl, lower alkylthio or mercapto
L linker:
- L = Q--Y--CₙH₂ₙ–(b)
- n = 1 to 4
- Y: direct bond or bivalent radical selected from:
- CO
- NHCO
- CONH
- CH═CH
- CR8(Q)
- C(OR6)(R7)
- O
- S
- SO2
- NR9
- Q: H, cycloalkyl, Ar1, di(Ar1)methyl, tri(Ar1)methyl; and when Y is not a direct bond, Q may also be lower alkyl or (Ar1)lower alkyl
- Ar1:
- phenyl optionally substituted with up to 3 substituents selected from halo, hydroxy, lower alkyl, lower alkyloxy, aminOsulfonyl, lower alkylcarbonyl, nitro, trifluoromethyl, amino, aminocarbonyl, phenylcarbonyl
- thienyl substituted with halo or lower alkyl
- Explicit exclusion: “provided that L is other than benzyl or substituted benzyl.”

Implication for scope: Claim 1 is broad in both (a) functional group inventory (R3/R4/R5) and (b) linker generation via Y/Q/n and Ar1 substitution, while still anchored by a specific stereochemistry and a defined piperidine cis-disubstitution.

2) Claim 4 defines a specific embodiment inside the genus

Claim 4 narrows to a discrete compound:

4-amino-5-chloro-N-2-methoxybenzamide plus:
- pharmaceutically acceptable acid addition salts
- stereochemical isomeric forms
- pharmaceutically acceptable quaternary ammonium salts

This is a species fallback that can be used to defend validity if the full genus is challenged on inventive step or novelty.

3) Claims 8 and 12 define another discrete embodiment tied to a particular L

Claim 8 recites:

4-amino-5-chloro-N-[1-[3-(4-fluorophenoxy)propyl]-3-methoxy-4-piperidinyl]-2-methoxybenzamide
and the same salt/isomer/quaternary ammonium extensions

Claim 12 recites the same compound family in the context of a composition claim.

Implication: The patent includes at least two “named” species structures in addition to the generic Markush scope: one relatively simple (Claim 4) and one tied to an aryl-ether propyl linker and para-fluorophenoxy (Claims 8/12).

How broad are R3/R4/R5 and what does that mean for freedom-to-operate?

1) Independent breadth in genus (Claim 1)

R3/R4/R5 are each independently selected from a wide list including:

small electronegative and ring-modifying groups: halo, hydroxy, cyano, nitro
basic/ionizable groups: amino, mono- and di(lower alkyl)amino
acylated/amide/sulfonamide-like motifs: aminocarbonyl, (Ar1)carbonylamino, lower alkylcarbonylamino, aminOsulfonyl
thio and sulfone/sulfinyl entries: lower alkylthio or mercapto, plus lower alkylsulfinyl/sulfonyl
ether and carbonyloxy: lower alkyloxy, lower alkylcarbonyloxy
carbonyl-like groups: lower alkylcarbonyloxy, and lower alkylcarbonyl

That breadth allows many direct analogs that preserve the GI motility pharmacophore while varying electronics and basicity.

2) Dependent claims narrow R3/R4/R5 to a smaller set

Claims 2/6/10/11 provide a constrained R3/R4/R5:

each independently selected from halo, amino, mono- and di(lower alkyl)amino, lower alkyloxy

Then Claims 3/7/11 specify a concrete triad:

R3 = methoxy
R4 = amino or methylamino
R5 = chloro
and positional attachment: “attached to the phenyl ring in the 2-, respectively 4- and 5-positions.”

Implication: From an infringement and design-around perspective, Claim 1 is the broad net. Claims 3/7/11 create a “focused corridor” of active analogs centered on methoxy-amino-chloro substitution, which can be used for both licensing and litigation leverage.

What is the functional scope of L (the linker) and where are the built-in carve-outs?

1) L has multiple structural families

L is generated by combining:

n = 1 to 4 (alkylene length)
Y selecting bond type or heteroatom/functional linkers (CO, NHCO, CONH, O, S, SO2, CH═CH, etc.)
Q selecting the terminal group identity, including aryl and arylalkyl forms
Ar1 as phenyl optionally substituted or thienyl

This architecture means the patent covers both:

simple heteroatom linkers (Y = O, S, SO2, NR9)
carbonyl-containing linkers (CO, NHCO, CONH)
direct or alkenyl linkers (direct bond, CH═CH)
branched substituent patterns via C(OR6)(R7) and CR8(Q) entries

2) Exclusion: benzyl and substituted benzyl

The explicit restriction:

“provided that L is other than benzyl or substituted benzyl.”

This is a meaningful design-around lever if a competitor’s candidate uses an actual benzyl-type L.

3) Additional claim-level Y constraints

Claims 13/14/15 further restrict Y to:

“Y is a direct bond, CO, NHCO, CONH, CH═CH, O, S, or SO2.”

So, if a competitor uses Y = a bivalent radical not in this set (like NR9 or certain Q–R8(Q) constructs), those dependent claims might not cover; however, Claim 1 still covers a broader Y set.

What are the method and composition claims, and how do they expand enforceable coverage?

1) Composition claims

Claim 5 is a unit dosage form composition:

“a pharmaceutical composition in unit dosage form comprising per dosage unit an effective gastro-intestinal motility stimulating amount”
of “a compound as described in claim 1” (with salt/isomer/quaternary ammonium coverage)

Claim 8 provides a composition species for a particular fluorophenoxy-propyl embodiment.

Claim 14 adds Y limitation within the composition context:

Y restricted to the subset: direct bond, CO, NHCO, CONH, CH═CH, O, S, SO2

2) Method claims

Claim 9 is a systemic administration method:

“method of stimulating the motility of the gastro-intestinal system”
by systemic administration to vertebrates of an “effective gastro-intestinal motility stimulating amount”
of the Claim 1 compound set

Claim 12 is the same method using the fluorophenoxy-propyl embodiment.

Claim 15 adds the Y limitation in the method context.

Implication: Even if a competitor only sells a formulation and not the isolated API, Claim 5/8 can still attach. If the competitor’s commercial package instructions align with the method claim (systemic administration for GI motility stimulation), Claim 9/12 create additional enforcement vectors.

How the dependent claim ladder maps to “defense in depth” for validity

The claim stack creates multiple potential “landing zones”:

Genus scope: Claim 1
Specific species (simple phenyl benzamide): Claim 4
Specific species (fluorophenoxy-propyl linker): Claims 8 and 12
Functional type narrowing:
- Y subset limitations: Claims 13 to 15
- R3/R4/R5 subset limitations: Claims 2, 6, 10, 11
Linker-specific narrowing on L:
- Claims 16-23 and 32-39 specify L as Ar1 O CₙH₂ₙ–(b) and further variations on R1 and n, including n = 3 examples.

This layered design is typical of patents aiming to preserve enforceability even if parts of the genus are challenged.

What is the practical claim coverage perimeter for competitor analogs?

1) Likely infringement zones (based on claim structure)

A candidate has higher risk if it matches all of the following:

has the cis configuration at piperidine positions 3 and 4
includes the benzamide / benzamide-like motif consistent with the formula definition in Claim 1
uses R1 within the Claim 1 list and R2 as H or lower alkyl
uses a phenyl substitution pattern for R3/R4/R5 that falls within the broad Claim 1 list, or within the more constrained “methoxy-amino-chloro” corridor (Claims 3/7/11)
uses an L that is not benzyl/substituted benzyl but is otherwise compatible with Q–Y–CₙH₂ₙ–(b)
is administered systemically for GI motility stimulation, or marketed as a unit dosage form containing effective amounts for that purpose

2) Primary design-around levers encoded in the claim text

Competitors often focus on one of the following:

piperidine stereochemistry: alter to non-cis configuration at positions 3 and 4 (Claim 1 requirement)
L = benzyl/substituted benzyl: use a benzyl-type linker even if it is otherwise close, to trigger the “L is other than benzyl” exclusion
Y out-of-set for dependent claims: use Y structures outside the constrained set used in Claims 13-15 and 14-15, though Claim 1 remains broad
R3/R4/R5 out-of-set: select substituents outside Claim 1’s R3/R4/R5 list; a competitor that only tweaks one position may still remain within the genus if the altered group still matches a listed category (e.g., many amines are still captured by mono/di(lower alkyl)amino)

What does the US patent landscape imply for other GI motility assets?

This analysis is limited to what can be concluded from the text provided for US 4,962,115. Without bibliographic details (filing date, assignee, priority, and related family members), it is not possible to produce a complete, sourced landscape of:

continuation/divisional relatives,
prosecution history events,
reexaminations,
or competing patents with comparable claim coverage.

No reliable, sourced cross-document mapping can be produced from the claim text alone.

Claim chart style summary: what each claim adds

Claim(s)	Scope role	Main incremental restriction/expansion
1	Genus definition	Cis 3,4 piperidine; broad R1/R2/R3/R4/R5; L = Q–Y–CₙH₂ₙ–(b); salts/isomers/quaternary ammonium; excludes benzyl-type L
2, 6	Genus subset for R3/R4/R5	R3/R4/R5 ∈ {halo, amino, mono-/di(lower alkyl)amino, lower alkyloxy}
3, 7, 11	Species-like R group corridor	R3 = methoxy; R4 = amino or methylamino; R5 = chloro at 2,4,5 phenyl positions
4	Specific chemical species	“4-amino-5-chloro-N-2-methoxybenzamide” plus salts/isomers/quaternary ammonium
5, 8	Composition	Unit dosage form with effective GI motility amount; species includes 4-fluorophenoxy-propyl embodiment (Claim 8)
9, 12	Method	Systemic administration to vertebrates for GI motility stimulation; species includes fluorophenoxy-propyl embodiment (Claim 12)
13-15	Y type limitation across claim categories	Y restricted to {direct bond, CO, NHCO, CONH, CH═CH, O, S, SO2}
16-23	L sub-form class and R1 interaction	L = Ar1 O CₙH₂ₙ–(b) and variations on R1 permitted
32-39	L and Y interaction refinement (methods/compositions)	L = Ar1 O CₙH₂ₙ–(b), plus n = 3 cases and R1 limits

Key Takeaways

US 4,962,115 claims a cis 3,4-disubstituted piperidine benzamide genus with extensive substituent freedom via R1/R2/R3/R4/R5 and a multi-parameter L linker (Q–Y–CₙH₂ₙ–(b), n = 1 to 4), while explicitly excluding benzyl and substituted benzyl as L.
The patent uses defense-in-depth: a broad genus (Claim 1) plus multiple dependent claim corridors (notably R3/R4/R5 methoxy-amino-chloro) and at least two discrete species embodiments (Claims 4 and 8/12).
Enforceability is expanded through separate claim categories: unit dosage compositions (Claims 5/8) and systemic administration methods for GI motility (Claims 9/12), each linked back to the core structural genus via claim dependency.
For freedom-to-operate, the highest-risk variants are those that preserve the cis stereochemistry and fall within the R3/R4/R5 substitution universe and L (non-benzyl) ether/hetero linker families; lower-risk variants are those that break the cis constraint or implement a benzyl-type L or substitute with groups outside the listed R categories.

FAQs

1) Does Claim 1 require a specific piperidine stereochemistry?

Yes. Claim 1 requires the substituents at the 3 and 4 positions of the piperidine ring to have the cis configuration.

2) What are the main substituent hotspots in the genus?

The main variables are R1, R2, and R3/R4/R5 on the aromatic and piperidine framework, plus the linker L = Q–Y–CₙH₂ₙ–(b).

3) Are salts and quaternary ammonium forms included?

Yes. Claim 1 includes pharmaceutically acceptable acid addition salts, stereochemical isomeric forms, and pharmaceutically acceptable quaternary ammonium salts.

4) What explicit L limitation appears in the claims?

The claim language excludes benzyl and substituted benzyl: “provided that L is other than benzyl or substituted benzyl.”

5) What clinical use scope do the claims cover?

The claims cover gastro-intestinal motility stimulation via systemic administration (method claims) and unit dosage forms (composition claims).

References

[1] United States Patent 4,962,115.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0076530	⤷ Start Trial	SPC/GB93/037	United Kingdom	⤷ Start Trial
Austria	16928	⤷ Start Trial
Australia	553845	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 4,962,115

Summary for Patent: 4,962,115