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Patent landscape, scope, and claims: |
United States Patent 6,313,146: Scope, Claim Coverage, and US Patent Estate for a Ca2+ Signaling Small-Molecule Amine Series
What is US Patent 6,313,146 and what does it claim at a high level?
US 6,313,146 claims a substituted chiral secondary amine scaffold (formula language using variables X1, X2, m, n) that is tied to biological activity: an increase in intracellular Ca2+ with specific EC50 thresholds measured in bovine parathyroid cells using a Cytosolic Ca2+ Cell Assay.
The claim set is built as:
- Broad structure claims (compound class defined by variable substituents and ring-fusion options).
- Narrower dependent coverage limiting substituent sets and parameter ranges (m, n).
- Specific compound exemplars by name/codenames (e.g., NPS R-568, R-4M, 4N, 4P, R-4V, R-4W, 6X, 21M).
- Functional potency claims requiring Ca2+ upshift with EC50 ≤ 5 µM (and dependent EC50 ≤ 1 µM).
- Composition claims for pharmaceutical compositions comprising the compounds (and at least one composition claims for compound 4W).
What is the chemical scaffold coverage in claim 1 of US 6,313,146?
Claim 1 defines “a compound having the chemical formula: [variable scaffold]” with:
- X1 and X2 = independently one or more substituents chosen from:
- Alkyl/alkoxy: CH3, CH3O, CH3CH2O
- Halogens: Br, Cl, F
- Fluoro/carbonyl/halofunctionals: CF3, CHF2, CH2F, CF3O
- Thio/protic/amine-adjacent: CH3S, OH, CH2OH, CONH2, CN
- Nitro: NO2
- Alkyls: CH3CH2, propyl, isopropyl, butyl, isobutyl, t-butyl
- Acetoxy/acetyl: acetoxy, acetyl
- Optional ring-fusion constraints:
- “two of X1 are together a fused cycloaliphatic ring, a fused aromatic ring or methylene dioxy”
- “two of X2 are together …”
- Parameter ranges:
- n between 0 and 5 inclusive
- m between 1 and 5 inclusive
- A proviso excludes a specific substitution combination:
- “provided that (X2), is not 3-t-butyl”
- Includes pharmaceutically acceptable salts.
How broad is that structurally?
The claim is broad in substituent identity and in allowed degrees of substitution (n and m ranges), with only targeted exclusion (3-t-butyl at the (X2) position referenced) and limited functional substituent families. The “two of X1 together form fused ring / methylene dioxy” language adds structural expansion beyond single substituent points.
How do dependent claims narrow the scaffold?
Substituent set narrowing
- Claim 2 tightens X1/X2 sets by removing some groups (e.g., it omits CONH2/CN/NO2 in the text you provided and limits to a smaller list).
- Claims 3–5 progressively limit the allowable substituent sets:
- Claim 3 includes CONH2, CN, NO2 and a subset of carbon/halogen groups.
- Claim 4 removes NO2, CN, CONH2 and further limits.
- Claim 5 reduces to Cl, F, CF3, CH3, CH3O.
Parameter narrowing
- Claim 6: n is 0 or 1.
- Claim 7: if n is 1, X2 is meta or ortho; X1 is meta.
- Claim 8: n is 1.
- Claim 9: X1 is meta.
Claim structure implication for design-around
- If a competitor stays outside the specific substituent set (e.g., uses a substituent not listed such as an amide not present in the lists, different halo patterns, or different functional groups), the dependent claim ladder may be avoided even if the broad claim 1 might still read.
- If a competitor uses allowed substituents but manipulates n or positional isomerism (e.g., avoids meta/ortho combinations tied to claims 7 and 9), the narrower coverage can fail while the generic structure coverage in claim 1 may still remain relevant.
What specific compounds are explicitly covered?
Claim 10 enumerates multiple specific named/codenamed structures, each tied to a formula:
“(R)-N-(3-arylpropyl)-1-(3-methoxyphenyl)ethylamine” with different aryl substitutions (2-chloro, 2-fluoro, 3-fluoro, 4-fluoro, 2-trifluoromethyl, 3-trifluoromethyl, 3-chloro, 3-(trifluoromethoxy)).
The exemplars you provided are:
- NPS R-467: (R)-N-(3-phenylpropyl)-1-(3-methoxyphenyl)ethylamine
- NPS R-568: (R)-N-(3-(2-chlorophenyl)propyl)-1-(3-methoxyphenyl)ethylamine
- R-4M: (R)-N-(3-(2-fluorophenyl)propyl)-1-(3-methoxyphenyl)ethylamine
- 4N: (R)-N-(3-(3-fluorophenyl)propyl)-1-(3-methoxyphenyl)ethylamine
- 4P: (R)-N-(3-(4-fluorophenyl)propyl)-1-(3-methoxyphenyl)ethylamine
- R-4V: (R)-N-(3-(2-trifluoromethyl)phenyl)propyl-1-(3-methoxyphenyl)ethylamine
- R-4W: (R)-N-(3-(3-trifluoromethyl)phenyl)propyl-1-(3-methoxyphenyl)ethylamine
- 6X: (R)-N-(3-(3-chlorophenyl)propyl)-1-(3-methoxyphenyl)ethylamine
- 21M: (R)-N-(3-(3-(trifluoromethoxy)phenyl)propyl)-1-(3-methoxyphenyl)ethylamine (your text shows “21M” with “3-(3-(trifluoromethoxy)phenyl)”)
Dependent compound claims
- Claims 11–18 lock those exemplars down individually (e.g., claim 11 to NPS R-568; claim 12 to NPS R-467; claim 13 to R-4M; claim 14 to 4N; claim 15 to 4P; claim 16 to R-4V; claim 17 to R-4W; claim 18 to 6X).
- Claim 19 adds 21M.
- Claims 46–54 mirror exemplar coverage in the composition context.
What potency/function coverage exists via Ca2+ EC50 claims?
The claim set introduces pharmacodynamic functional limitations:
- Claim 26: compound increases intracellular (Ca2+)i with EC50 ≤ 5 µM using:
- bovine parathyroid cells
- Cytosolic Ca2+ Cell Assay
- Claim 27: dependent EC50 ≤ 1 µM
Why this matters for scope
- A competitor could attempt to match the scaffold but argue their compounds do not meet the Ca2+ EC50 threshold. Functional limitations can narrow enforceability if potency is not met under the claimed assay conditions.
- Conversely, if a candidate is active in the same pathway at similar potency, the functional claims strengthen the patent’s ability to reach “equivalent structure with similar activity,” because the patent has a measurable endpoint.
What composition claims are included?
General composition coverage
- Claim 28: “A pharmaceutical composition” with pharmaceutically acceptable carrier plus therapeutically effective amount of a compound with the same scaffold and constraints as claim 1.
Additional dependent composition restrictions
Claims 29–45 narrow substituent sets and parameter ranges similar to the compound claims:
- Claim 33: n is 0 or 1
- Claim 34: X1 meta; if n=1 then X2 meta or ortho
- Claims 37–43 repeat X1=meta and n=1 or n≥1 type limitations in variants
- Claims 44–45 replicate the Ca2+ EC50 potency limitation in the composition context:
- EC50 ≤ 5 µM and dependent EC50 ≤ 1 µM.
Specific compound composition
- Claim 55: pharmaceutical composition comprising a therapeutically effective amount of compound 4W (as defined by your text), plus salt where applicable.
What additional structural variants appear in claims 20–25?
Claims 20–25 provide alternate structure emphasis:
- They allow “two of X1 together a fused benzene or methylene dioxy” and similarly for X2, with m at least 1.
- They constrain X1/X2 lists and then constrain n (e.g., n at least 1; “two of X1 together a fused benzene”; and X2 restricted to Cl, F, CF3, CH3, CH3O).
Scope implication
- These claims expand coverage to fused benzene / methylene dioxy embodiments, while still keeping the substituent universe relatively constrained.
What is the practical claim coverage map (who is in and who is out)?
Likely “in-scope” compounds
- (R)-1-(3-methoxyphenyl)ethylamine core with:
- N-substitution via a 3-arylpropyl chain (as shown in the enumerated compounds)
- Aryl ring bearing substituents restricted to the patent’s enumerated set (halogens, CF3/CF3O, CH3/CH3O, alkyls, etc.)
- Meeting parameter constraints for n and m as defined by the formula variables in the patent.
Likely “out-of-scope” approaches
- Using substituent chemistry not listed in the relevant dependent claim sets (notably in the narrower ladder claims).
- Substituting patterns that trigger the explicit exclusion for the referenced (X2) 3-t-butyl restriction.
- Compounds that match scaffold but do not meet the Ca2+ EC50 thresholds under the claimed assay conditions, weakening the EC50 functional claims (claims 26–27 and composition equivalents 44–45).
Patent landscape: what can be concluded from US 6,313,146 alone?
Your input contains only the claim text you transcribed. It does not include:
- assignee/applicant,
- priority filing data,
- prosecution history,
- listed related US patents,
- terminal disclaimers,
- family members,
- publication numbers,
- continuation/divisional records,
- Orange Book listings or FDA application linkage,
- litigation captions,
- settlements.
Under those constraints, a complete and accurate landscape covering:
- US continuation coverage,
- geographic family spread,
- granted vs. pending status by jurisdiction,
- Paragraph IV/biosimilar risks,
- expiration calculation,
- and litigation outcomes
cannot be produced.
Therefore, the only reliable, actionable landscape statement from the provided material is claim-scope based, not family or litigation based.
How strong is the patent estate for this scaffold based on claim mechanics?
Even without family data, US 6,313,146 shows several enforcement-relevant characteristics:
- Broad structural genus (claim 1) with enumerated substituent families and ring-fusion options.
- A claim ladder that tightens to smaller substituent and isomer subsets (claims 5–8, 7–9).
- Specific exemplars (claims 10–19) that are common “targets” for freedom-to-operate work, because many competitors and generic developers focus on named candidates rather than abstract variable scopes.
- Functional endpoint claims anchored to a specific biological assay in bovine parathyroid cells, providing a measurable potency discriminator (claims 26–27 and composition equivalents).
This combination increases the probability that a competitor facing a close chemical series cannot defeat the patent using a single argument (e.g., changing only substituent patterns), because structure claims and functional claims coexist.
Key takeaways
- US 6,313,146 claims a substituted chiral amine series defined by X1/X2 variable substituent families and parameters m (1–5) and n (0–5), plus a defined substitution exclusion relating to “(X2), not 3-t-butyl.”
- The patent includes broad compound coverage (claim 1), nested narrower dependent coverage (notably to n=0/1, X1=meta, and X2 positional constraints), and explicit enumerated exemplars including NPS R-568, R-4M, 4N, 4P, R-4V, R-4W, 6X, and 21M.
- Potency-limited functional claims require an increase in (Ca2+)i with EC50 ≤ 5 µM (and dependent ≤ 1 µM) in bovine parathyroid cells using a Cytosolic Ca2+ Cell Assay.
- Composition claims track the compound scope and reproduce EC50 limits for formulations.
- A full US patent landscape (family members, expiration dates, Orange Book status, Paragraph IV/biosimilar triggers, and litigation) cannot be derived from the provided claim text alone.
FAQs
- Do the EC50-dependent claims (claims 26–27) narrow infringement risk to potency-matching compounds?
- Which dependent claims most constrain substituent sets (e.g., claim 5 restricting X1/X2 to Cl/F/CF3/CH3/CH3O)?
- What is the significance of the explicit “(X2) is not 3-t-butyl” exclusion in claim 1?
- Are the specifically enumerated compounds (NPS R-568, R-4M, 4N, 4P, R-4V, R-4W, 6X, 21M) easier to assess for freedom-to-operate than generic formula coverage?
- How do composition claims (claim 28 and dependent claims 44–45) affect formulation-focused generic development?
References
- United States Patent 6,313,146 (claim text provided by user).
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