Details for Patent: 5,753,675

Summary for Patent: 5,753,675

Title:	Quinoline analogs of mevalonolactone and derivatives thereof
Abstract:	Quinoline analogs of mevalonolactone of the following formula are useful as anti-cholesterol synthesis agents: ##STR1## where the substituents are as defined in the specification.
Inventor(s):	Sompong Wattanasin
Assignee:	Novartis Pharmaceuticals Corp
Application Number:	US07/498,301
Patent Claim Types: see list of patent claims	Use; Composition;

Scope and Claims Analysis for US Patent 5,753,675, Plus the U.S. Patent Landscape and Freedom-to-Operate Implications

US Patent 5,753,675 is a U.S. small-molecule patent that claims a broad genus of cholesterol biosynthesis inhibitors defined by a core chemical formula plus tight constraints on substituent patterns and stereochemical variants. Claims also cover specific exemplified compounds and extend to methods of inhibiting cholesterol biosynthesis and treating atherosclerosis, plus pharmaceutical compositions.

Because the request is to analyze “scope and claims and patent landscape” for US 5,753,675, the claim-coverage analysis below is complete and specific to the claims you supplied. A reliable, jurisdiction-by-jurisdiction “landscape” (other patents, their claim scope, expiration dates, and litigation status) cannot be produced from claim text alone, so only the internal landscape implied by the claim structure is addressed.

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What does US 5,753,675 claim? (Genus structure, substituent limits, and covered embodiments)

Short answer: Claim 1 is a genus claim covering compounds of a defined formula where substituents R/Ro and ring substituents R1-R5 are limited by enumerated classes, and additional “proviso” limits restrict how many members of specific substituent types may appear within the set {R1,R2} and within the set {R3,R4,R5}. Claim 1 also contains conditions on X, Q, and a side-chain ester/cation system (Q and M), plus stereochemistry-dependent claim scope via dependent claims.

Claim 1 scaffold: formula + enumerated substituent classes

Claim 1 requires a compound of the form represented by the patent’s core structure (your ##STR38##), with these key structural constraints:

1. R and Ro are each independently one of:

   • C1–6 alkyl
   • C3–7 cycloalkyl

   • STR39## (a defined substituent fragment as shown in the patent)

2. R1–R5 are each independently one of:

   • hydrogen
   • C1–4 alkyl
   • C1–4 alkoxy
   • trifluoromethyl
   • fluoro
   • chloro
   • phenoxy
   • benzyloxy
   • hydroxy

3. Proviso limits (critical for narrowing the genus):

   • Not more than one of R1 and R2 is trifluoromethyl
   • Not more than one of R1 and R2 is phenoxy
   • Not more than one of R1 and R2 is benzyloxy
   • Not more than one of R1 and R2 is hydroxy
   • Not more than one of R3–R5 is trifluoromethyl
   • Not more than one of R3–R5 is phenoxy
   • Not more than one of R3–R5 is benzyloxy
   • Not more than one of R3–R5 is hydroxy

4. X is limited to two possibilities:

   • --(CH2)2 --
   • or --CH═CH--

This forces the linker/unsaturation pattern to be either fully saturated ethylene (CH2)2 or an ethenyl (vinyl) linkage.

5. Q and side-chain constraints introduce conditional coverage:
   • “##STR40## with the proviso that Q may be ##STR41## only when X is --CH═CH or R6 is C1–3 alkyl or both”
   • R6 is hydrogen or C1–3 alkyl (with the “only when” proviso controlling when Q can take that special form)
   • R7 is hydrogen
   • R8 is a physiologically acceptable and hydrolyzable ester group
   • M is a pharmaceutically acceptable cation

These requirements mean the claim is not simply a static structure. It is a dynamic set of constraints that tie (i) the vinyl vs saturated linker choice (X), (ii) the permissible identity of Q, and (iii) the permissible cation/ester system.

Dependent claims narrow further by examples and stereochemistry

Claim set continues to dependent claims that (i) select Q forms, (ii) specify stereochemistry, and (iii) lock R/Ro to particular aryl/alkyl embodiments.

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How broad is claim 1 in practice? (Genus breadth vs enumerated constraints)

Short answer: The genus is broad in scaffold coverage but narrowed by (1) hard limits on X, (2) hard limits on R7, (3) only hydrolyzable ester allowed for R8, (4) cation M limitation, and (5) “at most one” restrictions for specific polar/halogenated substituent classes within defined ring position subsets.

Substitute-class breadth

• Halogenation: Fluoro and chloro are permitted at R1–R5 with no explicit “at most one” rule for fluorine or chlorine. The “at most one” rule applies only to trifluoromethyl, phenoxy, benzyloxy, and hydroxy. So fluorine/chlorine substitution density could be higher, within independent substitution at each position.
• Alkyl/alkoxy: C1–4 alkyl and C1–4 alkoxy are permitted at each R1–R5 with no “at most one” restrictions.
• Hydroxy: limited to no more than one among the relevant groups (R1/R2 subset and R3–R5 subset).

X and Q linkage: a major claim limiter

Because X must be either --(CH2)2-- or --CH═CH--, any competitor with a different tether geometry (for example, longer chain, ether linkage, or heteroatom inclusion) is outside Claim 1.

The “only when” proviso for Q further restricts compound designs that use that special Q fragment: if Q is in the special form (##STR41##), the design must match either X=--CH═CH or R6=C1–3 alkyl (or both). Designs with X=--(CH2)2-- and R6=H cannot use that Q form.

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Which specific compounds are explicitly covered by US 5,753,675? (Dependent claims 2–7)

Short answer: The patent explicitly identifies particular ester salts and representative members of the genus by chemical description.

Claim 2 (Q and Z selection)

Claim 2 adds constraints:

• “Z is (a) and Q is ##STR42##” This indicates Claim 2 is an even narrower subset of Claim 1 where Z equals a specific option (a), and Q is fixed to a particular structure.

Claim 3 (3R,5S stereoisomer)

Claim 3 covers:

• a 3R,5S isomer within the Claim 2 framework (so stereochemistry is limited to that absolute configuration for that selected core subset).

Claim 4 (specific R and Ro choices)

Claim 4 covers genus members where:

• R and Ro are independently one of:
  • CH3
  • isopropyl
  • phenyl
  • 3,5-dimethylphenyl
  • 4-fluorophenyl

This narrows from Claim 1’s broad R/Ro classes (C1–6 alkyl, C3–7 cycloalkyl, or the fragment in ##STR39##) to a defined set of 5 options.

Claim 5–7 (named exemplified compounds)

Claim 5 lists three embodiments (and their sodium salts):

1. (E,)-6-heptenoic acid, 3,5-dihydroxy-7-(2-(1-methylethyl)-4-phenylquinolin-3-yl)ethyl ester, or sodium salt.
2. (E,)-6-heptenoate ester system described as part of the same line. (Your text compresses the exact IUPAC-style mapping; the key point is that Claim 5 includes an (E)-6-heptenoic acid-based ester and a specified quinolinyl dihydroxy ethyl ester motif.)

Claim 6:

• “7-(4-(3,5-dimethylphenyl)-2-methylquinolin-3-yl-)-3,5-dihydroxy-ethyl ester, or its sodium salt.”

Claim 7:

• “6-(2-(4-(3,5-dimethylphenyl)-2-methylquinolin-3-yl)-ethenyl!-tetrahydro-2H-pyran-2-one, or its sodium salt.” This claim text indicates a more complex ester or cyclic ester moiety (“tetrahydro-2H-pyran-2-one”) attached via the ethenyl linkage.

Practical implication: If a generic or competitor product uses any of these exact embodiments (or direct equivalents that still meet the structural claim terms), Claim 1 may already read broadly, but dependent claims provide “hard targets” for enforceability against close variants.

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What methods are protected? (Cholesterol biosynthesis inhibition and atherosclerosis treatment)

Short answer: Claims 8–10 provide functional therapeutic coverage: administering the claimed compounds for cholesterol biosynthesis inhibition, treating atherosclerosis, and compositions.

Claim 8: method of inhibiting cholesterol biosynthesis

• “administering to a mammal… an amount of a compound of claim 1” This is a classic method-of-treatment claim tied to the active compound identity.

Claim 9: method of treating atherosclerosis

• “administering… an effective amount… a compound according to claim 1” This adds a disease-state indication constraint.

Claim 10: pharmaceutical composition

• “cholesterol-biosynthesis inhibiting amount… + pharmaceutically acceptable carrier” Composition claims typically support formulation-based infringement even when method claims face evidentiary issues.

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How do the claim constraints affect generic design-around? (Key “non-infringement levers”)

Short answer: The most actionable design-around levers are the claim’s limited structural degrees of freedom: X must be one of two tether types, R7 must be hydrogen, R8 must be a hydrolyzable ester, and substituent “proviso” limits restrict multiplicity of trifluoromethyl/phenoxy/benzyloxy/hydroxy.

Highest-risk structural elements for infringement

1. X = --(CH2)2-- or --CH═CH--
2. R7 = hydrogen
3. R8 = physiologically acceptable and hydrolyzable ester group
4. M = pharmaceutically acceptable cation (so free acid forms may still fall in, if they can be construed as cation salts or if the claim construction reads onto the form used)
5. R1–R5 proviso multiplicity limits for specific substituent classes

Medium-risk elements

• R and Ro allowed classes (C1–6 alkyl; C3–7 cycloalkyl; fragment in ##STR39##) are fairly permissive.
• R6 is only hydrogen or C1–3 alkyl, with Q-form restrictions tied to X/R6.

Lower-confidence design-around without full formula mapping

The core formula in the patent depends on labeled substituent placements (R, Ro, R1–R5, Z, Q, etc.). Without the rest of the drawing-level definitions, the safe conclusion is that any competitor must still avoid satisfying all claim term limitations, not just one.

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What is the “patent landscape” implied by this claim set? (Internal landscape: what other claims usually exist)

Short answer: Based on the claim architecture alone, the estate likely contains:

• a broad genus claim (Claim 1),
• narrower dependent claims by stereochemistry and specific substituent selections (Claims 2–7),
• therapeutic method claims (Claims 8–9),
• formulation/composition claims (Claim 10).

Without the application publication, specification, and prosecution history, this is the only defensible landscape read.

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Key Takeaways

• US 5,753,675 Claim 1 is a structured genus defined by a core formula with hard constraints on tether identity (X), ester requirements (R8 hydrolyzable ester), and substituent multiplicity limits for trifluoromethyl, phenoxy, benzyloxy, and hydroxy within defined position sets.
• Dependent claims carve out enforceable subsets: a fixed Q/Z subset (Claim 2), a specific stereoisomer (Claim 3), defined R/Ro options (Claim 4), and explicitly described exemplified ester embodiments and their sodium salts (Claims 5–7).
• Therapeutic claims extend protection to method-of-use for cholesterol biosynthesis inhibition and atherosclerosis treatment, plus composition claims.
• Most effective design-around vectors are altering tether identity (X), removing the required ester/cation system (R8/M), changing stereochemistry where relevant, and avoiding prohibited substituent multiplicity patterns.

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FAQs

1) Does US 5,753,675 require a specific ester linkage to infringe?
Yes. Claim 1 requires R8 to be a physiologically acceptable and hydrolyzable ester group, and Claim 1 also requires M to be a pharmaceutically acceptable cation.

2) What parts of the claim are most likely to defeat infringement on structural grounds?
The claim’s hard-limited tether (X only --(CH2)2-- or --CH═CH--) and the “at most one” provisos for certain substituent classes (trifluoromethyl/phenoxy/benzyloxy/hydroxy) in the specified position sets.

3) Are stereoisomers covered even if the compound name differs?
Claim 3 specifically targets the 3R,5S isomer within the Claim 2 subset. If a product is outside that stereochemical configuration while still meeting other structure terms, Claim 3 would not apply, but Claim 1 may still apply if the compound otherwise falls within the genus.

4) Are sodium salts explicitly included?
Yes. Claims 5–7 state the relevant embodiments or its sodium salt.

5) Do the therapeutic claims cover administration regardless of the disease mechanism evidence?
The method claims (Claims 8–9) are tied to administering a compound of Claim 1 for cholesterol biosynthesis inhibition or for treating atherosclerosis, without adding an additional mechanism-of-action limitation beyond that use.

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References (APA)

No external sources were cited because the request supplied only claim text and did not provide the patent’s bibliographic identifiers, publication numbers, or any authoritative landscape documents.

Drugs Protected by US Patent 5,753,675

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate