Details for Patent: 5,385,929

Summary for Patent: 5,385,929

Title:	[(Hydroxyphenylamino) carbonyl] pyrroles
Abstract:	2-(4-Fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(hydroxyphenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid, and their lactone forms, and salts and solyates thereof, inhibit cholesterol biosynthesis, and thus are useful in treating hypercholesterolemia.
Inventor(s):	Susan M. Bjorge, Ann E. Black, Bruce D. Roth, Thomas Woolf
Assignee:	Warner Lambert Co LLC
Application Number:	US08/238,120
Patent Claim Types: see list of patent claims	Use; Composition; Formulation;

Scope and Claims Analysis for US Patent 5,385,929: What Compounds, Formulations, and Methods Are Covered and Where the Patent Estate Is Vulnerable

US Patent 5,385,929 is a small-molecule composition-and-method patent built around a core chemical formula that is then narrowed by stereochemistry and substituent identity. The independent claim 1 covers a genus defined by a structural formula, including protected hydroxy substituents (via R1) and “solyates” plus open-chain equivalents. Dependent claims 2–11 narrow the genus to specific R1 choices (benzyl or hydrogen) and then to specific enumerated compounds with defined stereochemistry and substitution patterns. Claims 12–15 cover pharmaceutical formulations containing claim 1 compounds, and claims 16–18 cover cholesterol-synthesis inhibition and treatment of hypercholesterolemia via administration.

The estate scope is therefore split into (i) broad genus coverage at claim 1, (ii) narrow product-at-issue coverage at dependent claims with fully specified structures, and (iii) functional therapeutic coverage tied to administration of the same claimed chemical entities.

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What does US Patent 5,385,929 claim 1 cover: genus scope, solyates, and “open chain” equivalents?

Featured snippet answer: Claim 1 covers compounds having a defined structural formula where substituent R1 is hydrogen or a hydroxy-protecting group, including solvates (referred to as “solyates”), and also includes an open-chain form of an alternative structural expression, plus pharmaceutically acceptable salts and solvates.

Claim 1 elements that control infringement scope

1. Core structural formula (closed-form and open-chain variants)

   • Claim 1 is drafted to cover compounds that fall within a structural formula labeled in the patent as a “formula ##STR17##”.
   • It also explicitly includes the open chain form of the formula ##STR18##, meaning the patent does not restrict coverage only to one tautomeric or cyclized representation.

2. R1 definition: hydrogen or a hydroxy-protecting group

   • The only explicit variable called out in claim 1 is R1.
   • R1 is limited to:
     • hydrogen, or
     • a hydroxy protecting group.
   • This language matters for design-around. If a competitor uses a hydroxyl-protecting group not considered within the patent’s definition of “hydroxy protecting group,” claim coverage could narrow. If it is a standard protecting group (e.g., benzyl protecting group is expressly recited later), coverage is more likely.

3. Solyates and salts

   • Claim 1 covers “solyates thereof” (synthesizing with standard patent usage, these are solvates formed with solvents).
   • It also covers pharmaceutically acceptable salts and solvates.
   • This expands coverage beyond the free base/neutral form to salt forms used in drug development.

4. Inclusion of “solyates” alongside the open-chain form

   • Solvate coverage combined with open-chain inclusion makes claim 1 broader across physical form strategies (e.g., crystallization from different solvents) and dynamic equilibria between structural depictions.

Practical claim 1 takeaway

• Claim 1 is a genus claim with one principal substituent variable (R1) plus generic inclusion of solvates and salts.
• The open-chain clause reduces the ability to avoid infringement by claiming that a candidate exists predominantly in a different conformational form, at least as represented by the patent’s “open chain form” formula.

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How narrow are claims 2–11: do they cover specific stereoisomers and hydroxyl substitution patterns?

Featured snippet answer: Yes. Claims 2–11 progressively narrow claim 1 by specifying R1 (benzyl or hydrogen) and then enumerating specific stereochemical compounds with full substituent identity, including different hydroxyphenyl substitution patterns (para-, meta-, or ortho- relative positions as reflected in the named hydroxyphenyl group) and specific salt forms (sodium salts for the “claim 8” branch).

Claim 2 and claim 3: the first narrowing step

• Claim 2: R1 is benzyl.
• Claim 3: R1 is hydrogen.

This indicates the patent recognizes at least two practical classes of embodiments:

• protected hydroxyl embodiments (benzyl as an example),
• deprotected hydroxyl embodiments (hydrogen).

Claims 4–7: R1 = hydrogen, then “formula ##STR19##” plus specific substituted hydroxyphenyl variants

• Claim 4: The compound of claim 3 which is formula ##STR19## (structural specification beyond “R1”).
• Claims 5–7: specify the compound of claim 4 with explicit stereochemistry (2R-trans) and detailed substituent identity:
  • Claim 5: N-(4-hydroxyphenyl) substitution.
  • Claim 6: N-(3-hydroxyphenyl) substitution.
  • Claim 7: N-(2-hydroxyphenyl) substitution.

All three share the same core scaffold with:

• a 4-fluorophenyl substituent,
• an (1-methylethyl) group,
• a 4-phenyl group,
• and a shared tetrahydro-hydroxy-oxo pyran motif in the side chain as expressed in the claim.

Scope implication: Claims 5–7 cover three positional isomer variants on the hydroxyphenyl group attached through an anilide/urea-like linkage to N. This is a classic “family within a family” pattern: broad claim 4 plus explicit capture of ortho/meta/para hydroxyphenyl embodiments in claims 5–7.

Claims 8–11: another narrowed branch with β,δ-dihydroxy and sodium salts

• Claim 8: the compound of claim 3 which is formula ##STR20## or a pharmaceutically acceptable salt thereof.
• Claims 9–11: specify sodium salts with full stereochemistry [3R,5R] and a defined substituted aromatic amino linkage:
  • Claim 9: 4-hydroxyphenylamino carbonyl motif, with naming showing “4-[(4-hydroxyphenylamino)carbonyl]”.
  • Claim 10: 3-hydroxyphenylamine variant (“(3-hydroxyphenylamine)carboxyl”).
  • Claim 11: 2-hydroxyphenylamine variant (“(2-hydroxyphenylamino)carbonyl”).

Scope implication: These claims capture a second cluster of embodiments where the functional group relationships and salt state are fixed (sodium salts explicitly recited in 9–11). A competitor changing salt form may still fall under “pharmaceutically acceptable salts” language in claim 8, but claims 9–11 are explicit to sodium salts.

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Do the formulation claims 12–15 extend protection beyond the active chemical entity?

Featured snippet answer: Yes. Claims 12–15 add a formulation layer: a pharmaceutical formulation comprising a claim 1 compound with a pharmaceutically acceptable carrier, and then narrow to R1 = hydrogen and to particular active ingredient structures within claims 13–15.

Claim-by-claim formulation scope

• Claim 12: “A pharmaceutical formulation comprising a compound of claim 1 together with a pharmaceutically acceptable carrier.”

  • This is broad across any formulation format that uses a claim 1 compound.

• Claim 13: formulation where active ingredient has R1 = hydrogen (ties to claim 3 branch).

• Claim 14: formulation where active ingredient is formula ##STR21## (specific structure).

• Claim 15: formulation where active ingredient is formula ##STR22## or pharmaceutically acceptable salts.

Scope implication: If a product uses a claim 1 genus compound in any carrier system, it can meet claim 12. If the active is constrained to specific R1 = hydrogen structures, claims 13–15 provide tighter coverage.

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What therapeutic methods are protected: inhibition of cholesterol synthesis and treatment of hypercholesterolemia?

Featured snippet answer: Claims 16–18 protect administration of claim 1 compounds to animals for inhibiting cholesterol synthesis, and to mammals for treating hypercholesterolemia.

Claim 16–18 structure

• Claim 16: “A method of inhibiting cholesterol synthesis in an animal comprising administering a compound of claim 1.”
• Claim 17: same method employing a compound where R1 = hydrogen.
• Claim 18: “A method of treating a mammal suffering from conditions of hypercholesterolemia by administering a compound of claim 1 wherein R1 is hydrogen.”

Scope implication

• These are method-of-use claims limited by:
  • the therapy objective (cholesterol synthesis inhibition; hypercholesterolemia treatment),
  • the administration of a specific class of compounds (claim 1, and in 17–18 R1 = hydrogen).
• Design-around by changing the method of administration or therapeutic endpoint can matter, but direct competitor products with the same intended use and drug identity likely remain within the claim frame if a claim 1 compound is administered.

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How does the claim architecture affect freedom-to-operate: genus vs enumerated embodiments

Featured snippet answer: Claim 1 is broad (genus + salts/solvates + open-chain equivalents), while dependent claims 5–7 and 9–11 identify fully specific embodiments. A generic or alternative salt/formulation that stays within the claim 1 chemical genus can still face infringement on claim 1 even if it avoids the specific structures in dependent claims.

Infringement risk ladder

1. Highest risk: products containing a compound within claim 1, including solvates/salts and open-chain equivalents.
2. High risk within claim 1: if product uses R1 = hydrogen, it maps into multiple dependent branches (claims 3, 4, 5–7, 8–11, 13–15, 17–18).
3. Even if circumventing one branch: if the compound is still within the R1 definition (hydrogen or hydroxy-protecting group), claim 1 remains a target.

Design-around pressure points

• R1 selection: since claim 1 allows hydrogen or “hydroxy protecting group,” a competitor seeking avoidance must operate outside that definition or outside the structural formula. The dependent explicit “benzyl” coverage in claim 2 suggests benzyl is within the intended scope.
• Salt/solvate form: claim 1 explicitly includes pharmaceutically acceptable salts and solvates, reducing the value of changing crystallization solvent unless the new form falls outside “pharmaceutically acceptable” or outside the patented compound identity.
• Open-chain form: inclusion reduces avoidance based on cyclized/open-chain representational differences.

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What patent landscape questions matter for US 5,385,929: strength, expiration drivers, and generic or biosimilar entry?

Featured snippet answer: The enforceable scope of US 5,385,929 turns on whether the accused product is within claim 1’s genus (formula + R1 definition + open-chain equivalents + salts/solvates). Entry strategies that avoid the genus, change active ingredient identity beyond the claim structure, or operate outside the covered method-of-use can reduce risk. Biosimilar risk is not applicable because the patent is for a small molecule (not a biologic).

Generic entry risks

• If the active ingredient is a compound that matches the claim 1 formula with R1 = hydrogen or hydroxy-protecting group, the risk is direct for composition and formulation.
• If the generic uses the same active ingredient but different formulation, claim 12 still targets formulation with a pharmaceutically acceptable carrier.

Method-of-use risk

• If a competitor’s label or clinical use is hypercholesterolemia/cholesterol synthesis inhibition by administering the same compound, claims 16–18 may add exposure even when composition claims are disputed.

Timing and exclusivity

• Determining the exact expiration date and Orange Book exclusivity status cannot be done from the claim text alone; those depend on filing/priority dates, patent term adjustment, and whether the patent is listed for a specific FDA-approved product. Without that data, no expiration timeline can be provided.

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Key takeaways

• Claim 1 is the core: it covers a genus defined by a chemical formula with R1 = hydrogen or a hydroxy-protecting group, plus solvates (“solyates”), pharmaceutically acceptable salts, and an open-chain form.
• Claims 2–11 narrow into specific embodiments: explicit dependence on R1 = benzyl or hydrogen, and then fully specified stereochemistry and hydroxyphenyl positional isomers (claims 5–7) and sodium-salt embodiments (claims 9–11).
• Formulations are covered: claims 12–15 add protection for pharmaceutical formulations using claim 1 compounds, including narrowed R1 = hydrogen structures.
• Methods-of-use are covered: claims 16–18 protect cholesterol synthesis inhibition and hypercholesterolemia treatment via administration of the claimed compounds.
• Practical FTO conclusion: any competitor product using a small molecule that falls within claim 1’s formula and R1 definition carries composition/formulation exposure; changing formulation or salt/solvate alone is unlikely to avoid claim 1 coverage.

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FAQs

What parts of US 5,385,929 are most likely to be asserted against generics?

The composition genus in claim 1 and the formulation coverage in claim 12 are the most direct hooks, with method-of-use claims (16–18) used to support infringement theories aligned with labeled indications.

Do the claims protect specific stereochemistry only?

No. Claim 1 is genus-level, but several dependent claims explicitly require stereochemical descriptors such as (2R-trans) and [3R,5R], making those embodiments tightly defined.

Does changing the salt or solvate avoid infringement?

Claim 1 includes pharmaceutically acceptable salts and solyates, so simply selecting a different salt or solvate used to formulate the same compound generally does not remove claim coverage.

Are benzyl-protected hydroxy versions covered?

Yes. Claim 2 explicitly states R1 = benzyl, which is a clear indication that benzyl-protected embodiments fall within the patent’s covered scope.

Is there biosimilar risk from this patent?

No. The claims are directed to small-molecule chemical entities and their formulations and administration methods, not biologics. Biosimilar-specific risk frameworks do not apply to this patent.

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References (APA)

1. U.S. Patent No. 5,385,929.

Drugs Protected by US Patent 5,385,929

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

International Family Members for US Patent 5,385,929

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	209203
Germany	69523978
Denmark	0680963
European Patent Office	0680963
Spain	2168318
Japan	3316661
Japan	H07304735