Details for Patent: RE42462

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Summary for Patent: RE42462

Title:	Carboxylic acid derivatives, their preparation and use
Abstract:	Carboxylic acid derivatives where R-R6, X, Y and Z have the meanings stated in the description, and the preparation thereof, are described. The novel compounds are suitable for controlling diseases.
Inventor(s):	Hartmut Riechers, Dagmar Klinge, Wilhelm Amberg, Andreas Kling, Stefan Muller, Ernst Baumann, Joachim Rheinheimer, Uwe Josef Vogelbacher, Wolfgang Wernet, Liliane Unger, Manfred Raschack
Assignee:	Royalty Pharma Collection Trust
Application Number:	US12/481,594
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent RE42462
Patent Claim Types: see list of patent claims	Compound;

US RE42462 (U.S. Drug Patent Re.42462): Scope of Claims and US Patent Estate for the Formula I Compound Family

US RE42462 is a reissue that inherits a broad Markush-style claim strategy around Formula I compounds, defined by a dense matrix of substituent variables (R, R1/R2/R3/R4/R5/R6, and ring-heteroatom variables Y and Z). The claims are written to capture a large chemical space by allowing many alternative substituents, including acidic bioisosteres (carboxylic acid and hydrolyzable CO2H precursors), heteroaromatic and cyclic replacements, and wide ranges of alkyl/aryl substitution. Dependent claims then progressively narrow to common commercial “anchor” embodiments (notably R = CO2H, X = CH (X as CR14 with R14 = H), Y = O, Z = O, and di-phenyl (R4/R5 = phenyl), with R2/R3 = C1–C4 alkyl and R6 = C1–C8 alkyl).

What is the scope of US RE42462 claims covering Formula I substituents?

Short answer: RE42462 claim 1 is a broad genus claim to “Formula I” with substituent variables that permit many carboxylate prodrug forms, multiple aryl substitution patterns, and multiple ring/heteroatom embodiments through Markush alternatives for R, X/Y/Z, and R4/R5/R6. Dependent claims define tighter subgenera that align with specific “preferred” chemistry.

Claim 1: core variables and what each does to coverage

Claim 1 defines:

• R: formyl; tetrazole; nitrile; —CO2H; or a radical hydrolyzable to —CO2H.
• R2: H, hydroxyl, amines/amidoalkyls, halogens, C1–C4 alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio.
• X: CR14, where R14 = H or C1–C5 alkyl. (This controls whether the position is a hydrogen-substituted methine versus a methyl/alkyl-substituted methine.)
• R3: H, hydroxyl, amines/amidoalkyls, halogens, C1–C4 alkyl, haloalkyl, alkoxy, haloalkoxy; and additional ring-closure participation where CR3 is linked to CR14 to form a 5- or 6-membered ring.
• R4 and R5: each phenyl or naphthyl, substituted with broad allowable groups; or connected/“ortho-coupled” aryl topology via direct linkage or heteroatoms/linkers; or replaced by C3–C7 cycloalkyl; or replaced by a five- or six-membered heteroaromatic moiety with defined heteroatom sets and optional substituents (including halogens and C1–C4 alkyl/alkoxy/alkylthio/phenoxy/phenylcarbonyl).
• R6: H or broad alkyl/alkenyl/alkynyl/cycloalkyl with substitution by another layer of defined groups (halogen, alkoxy, alkylthio, alkylcarbonyl/alkoxycarbonyl, amino, phenyl/phenoxy, and substituted phenyl/phenoxy patterns).
• Y: sulfur, oxygen, or a single bond.
• Z: sulfur, oxygen, —SO—, or —SO2—.

Impact for claim coverage: This is not a “single scaffold” claim. It is a genus claim that lets competitors potentially argue non-infringement by altering at least one of:
(1) the acidic pharmacophore logic (R); (2) the X/R14 identity; (3) Y/Z oxidation state / heteroatom choice (O vs S vs sulfoxide/sulfone vs single bond); or (4) the aryl/heteroaryl core represented by R4/R5 (including ring connectivity and heteroaromatic replacement).

Claim 2 to Claim 10: narrowing to specific subgenera

• Claim 2: X = CR14 and R14 = H → collapses one branch of X.
• Claim 3: R = CO2H (locks the acidic group to the free acid rather than alternative hydrolyzable forms).
• Claim 4: R2 = methoxy and R3 = methoxy.
• Claim 5: R4 = phenyl and R5 = phenyl.
• Claim 6: R6 = C1–C8 alkyl.
• Claim 7: Y = oxygen.
• Claim 8: Z = oxygen or sulfur.
• Claim 9: Z = oxygen.

Claim 10 is a “fully specified preferred embodiment” combination:

• X = CH
• Y = O
• Z = O
• R = CO2H
• R2 = methoxy
• R3 = methoxy
• R4 = phenyl
• R5 = phenyl
• R6 = methyl/ethyl/iso-propyl.

Impact: Claim 10 is a high-value dependent claim because it is both narrow and internally consistent (single H on X, O/O for Y/Z, free acid, di-phenyl, and methyl/ethyl/propyl at R6).

Claim 11 and Claim 15 to Claim 21: broadening R and alternative R-group logic

• Claim 11 expands R to multiple alternatives including tetrazole, nitrile, and “radical where R1 has…” highly detailed substituent sets (including succinylimidoxy; multiple heteroaromatic ring linkers; and other prodrug-like or linkage substituents).
• Claim 15 is another broad dependency from claim 1 that sets many other variables: R allowed among formyl/CO2H/hydrolyzable CO2H; R2 = C1–C4 alkyl; X = CR14 with R14 = H; R3 = C1–C4 alkyl; and specifies the kinds of R4/R5 and R6 allowed, and Y/Z options.

Claims 12 to 14 and 16 to 20: “classic preferred” carbonic acid + di-phenyl + oxygen/sulfur topologies

• Claim 12: R = CO2H framework with R4/R5 = phenyl.
• Claim 13: X = CH, Y = O, Z = O, R = CO2H, R2 = C1–C4 alkyl, R3 = C1–C4 alkyl, R6 = C1–C8 alkyl.
• Claim 14: R2 = methyl and R3 = methyl.
• Claim 16: more explicit for R4/R5 substituted phenyls and R6 substituted alkyls, plus Y=O and Z=O.
• Claims 17-19: variations around R4/R5.
• Claim 20: expands X side to R14 = H or C1–C5 alkyl, and broadens Z to sulfor or oxygen (Z = sulfor/oxygen).

Claims 21 to 25: alternative Y/Z = S/O options and expanded R2/R3 halogen/alkyl/hallkyl

• Claim 21: allows R to be CO2H/hydrolyzable CO2H; R2 and R3 can be halogen, C1–C4 alkyl, or haloalkyl; R4/R5 substituted phenyl; R6 optional H or C1–C8 alkyl/cycloalkyl; Y sulfur or oxygen; Z sulfur or oxygen.
• Claim 22: very specific list for R (including methyl/tert-butoxy/alkenylcarboxylate-like options and amide/other carboxylate derivatives), plus R2 and R3 set to specific halogen/alkyl/hyper-substitution patterns. Also restricts Z/Y to sulfur/oxygen.
• Claims 23-25: further narrow R4/R5 and rest.

How broad is RE42462 claim 1 in infringement-risk terms?

Short answer: Claim 1 is broad enough to capture many “analog” designs, but infringement risk hinges on whether a competitor stays within the allowed R acid/prodrug set and Y/Z heteroatom topology, and whether the aryl/heteroaryl portion matches the allowed R4/R5 options (including specific linkage possibilities).

Claim breadth drivers

1. Acid pharmacophore breadth (R):

   • Free carboxylic acid (—CO2H) plus hydrolyzable precursors.
   • Also alternative “acid-like” rings/groups such as tetrazole and nitrile, which can be used as carboxylate bioisosteres.

2. X and ring-closure (X/R3 coupling):

   • X is either methine with R14 = H or C1–C5 alkyl.
   • R3 can participate to form a 5- or 6-membered ring where CR3 links to CR14.
   • Competitors altering that geometry can potentially move out of literal coverage.

3. Heteroatom topology Y/Z (particularly high leverage):

   • Y can be S, O, or single bond.
   • Z can be S, O, —SO—, or —SO2—.
   • Designs with different oxidation state or atom presence may avoid coverage if they fall outside these explicit alternatives.

4. Aryl/heteroaryl freedom (R4/R5):

   • Large Markush ranges allow phenyl/naphthyl substitution patterns, ortho connectivity through direct linkage or through heteroatoms/linkers, and replacement by cycloalkyl or defined heteroaromatics.

Which dependent claims define the most commercially relevant “preferred” embodiments?

Short answer: The most commercially relevant subgenera are the oxygen/oxygen topologies and free acid versions with di-phenyl at R4/R5 and alkyl at R2/R3/R6.

Preferred subgenera cluster (from the text provided)

• R = CO2H, X = CH, Y = O, Z = O, R4 = phenyl, R5 = phenyl
  • Claim 10 (includes R2=MeO, R3=MeO, R6=Me/Et/iPr)
  • Claim 13 (R2/R3 = C1–C4 alkyl; R6 = C1–C8 alkyl)
  • Claim 16 (R2/R3 = C1–C4 alkyl; R4/R5 substituted phenyl; R6 substituted alkyl; Y=O; Z=O)
  • Claim 24/25 restate the same narrow scaffold with specific variable caps (R2 and R3 alkyl; R6 alkyl; di-phenyl).

Acid alternative subgenus

• R = hydrolyzable CO2H or other R groups (tetrazole/nitrile/formyl; detailed prodrug radicals) appear in:
  • Claim 1 (genus)
  • Claim 11 and Claim 15 and Claim 18
  • Claim 21/22 (more specified alternatives including listed carboxylate/prodrug-like structures).

What patent estate issues flow from a reissue like RE42462 (claim scope vs priority)?

Short answer: A reissue can reframe claim scope while maintaining priority, and the presence of expansive Markush definitions suggests the assignee sought to preserve broad genus protection against design-around. From a freedom-to-operate lens, the main estate risk is that the dependent “anchor” claims (CO2H + X=CH + Y=O + Z=O + di-phenyl) can be asserted even if the competitor changes less critical substituents within the allowed bands.

When does RE42462 lose exclusivity in the US?

No exclusivity timeline can be computed from the claim text alone. Nothing in the provided material includes the patent’s filing date, earliest priority date, reissue date, PTA, or any Orange Book-listed drug linkage, so a correct exclusivity/expiration schedule cannot be produced.

What Orange Book status does RE42462 have for which drug?

No Orange Book listing, application number, NDA/BLA link, or Orange Book patent codes (type “P”, “B”, “N”) are provided. The drug identity and Orange Book status cannot be determined from the claim text alone, so status analysis would be incomplete.

What generic entry risks exist for products covered by RE42462?

Risk depends on three items not provided here: the specific marketed drug, strength(s)/dosage forms, and whether there are Paragraph IV (ANDA) or 505(b)(2) challenges tied to RE42462 in the Orange Book. With those missing, a quantified entry-risk scenario cannot be produced.

How strong is the patent’s claim coverage against structural design-arounds?

Likely “design-around” levers

Based on the explicit claim structure, competitors can target these boundaries:

1. Swap Y/Z topology

   • Example lever: use a single-bond or oxygen-only vs sulfur-inclusive pattern outside the allowed alternatives.
   • Another lever: avoid sulfoxide (—SO—) and sulfone (—SO2—) if the competitor uses different sulfonamide/sulfamate-like motifs, or if the sulfur state differs from the allowed set.

2. Change the acidic group logic (R)

   • Staying within R alternatives keeps risk high.
   • Exiting R alternatives (e.g., moving away from CO2H and hydrolyzable CO2H prodrugs, tetrazole, nitrile, formyl) reduces literal coverage.

3. Alter the X/R14 substitution pattern or ring formation

   • X is constrained to CR14 with R14 = H or C1–C5 alkyl.
   • If substitution exceeds C1–C5 or changes ring connectivity such that R3 cannot link to CR14 to yield a 5- or 6-membered ring as claimed, literal coverage can weaken.

4. Modify R4/R5 aromatic topology

   • R4/R5 are constrained to phenyl/naphthyl substituted patterns, specific ortho coupling arrangements, cycloalkyl (C3–C7), or defined heteroaromatic moieties.
   • New cores outside these classes create stronger non-infringement arguments.

Litigation posture signals from the claim design

The nested dependent structure and multiple alternative pathways for R and heteroatom topology suggest the drafter anticipated infringement theories across multiple subgenera. A narrow competitor design can still fall within at least one dependent cluster if it retains:

• free acid or hydrolyzable CO2H,
• oxygen/oxygen (or sulfur/oxygen) Y/Z,
• di-phenyl (or equivalent R4/R5 allowed aryl connectivity),
• and alkyl banding for R2/R3/R6.

Which companies are challenging RE42462 and what litigation affects entry?

No litigant identities, case captions, or dockets are provided. No party-specific litigation analysis can be generated from the supplied content.

Key Takeaways

• RE42462 claim 1 is a high-coverage Formula I genus built from Markush variables across the acid/prodrug group (R), methine substitution (X/R14), aromatic/heteroaromatic substitution topology (R4/R5), side-chain substitution (R6), and key heteroatom oxidation-state positions (Y and Z).
• The most enforceable “anchor” subgenera in the text provided are those combining R = CO2H, X = CH (R14 = H), Y = O, Z = O, and R4/R5 = phenyl, with R2/R3 alkyl and R6 = alkyl (Claims 10, 13, 16, 24/25).
• The primary design-around paths implied by the claim text are:
  (1) alter R away from the allowed CO2H/hydrolyzable CO2H/tetrazole/nitrile/formyl set,
  (2) change Y/Z topology or oxidation state away from the enumerated choices,
  (3) move X/R14 outside the allowed H or C1–C5 alkyl pattern and/or ring-closure possibility, and
  (4) replace the allowed R4/R5 aromatic/heteroaromatic motifs and ortho-linkage classes.

FAQs

1. Does RE42462 cover carboxylic acid prodrugs if R is hydrolyzable to CO2H?
   Claim 1 expressly includes “a radical which can be hydrolyzed to COOH” as an R option, and dependent claims preserve this concept in broader R variants.

2. Are sulfoxide and sulfone forms covered via Z?
   Yes. Claim 1 lists Z as sulfur, oxygen, —SO—, or —SO2—.

3. Is X fixed to CH or can X be alkyl-substituted?
   Claim 1 allows X = CR14 where R14 is hydrogen or C1–C5 alkyl. Dependent claim 2 narrows to R14 = H (X = CH).

4. Can R4 and R5 be heteroaromatic rather than phenyl/naphthyl?
   Yes. Claim 1 allows R4/R5 to be replaced by defined five- or six-membered heteroaromatic moieties with specified heteroatom counts and substituent ranges.

5. Which dependent claims specify the tightest oxygen/oxygen and di-phenyl pattern?
   In the provided claim set, Claims 10, 13, 16, 24, and 25 jointly define the oxygen/oxygen (Y = O, Z = O), CO2H, and di-phenyl R4/R5 subspace with alkyl caps for R2/R3/R6.

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References (APA)

No external sources were cited because no bibliographic details (patent title/assignee/filing/reissue dates), Orange Book entries, or litigation dockets were provided in the input.

Drugs Protected by US Patent RE42462

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

Foreign Priority and PCT Information for Patent: RE42462

PCT Information
PCT Filed	October 07, 1995	PCT Application Number:	PCT/EP95/03963
PCT Publication Date:	April 25, 1996	PCT Publication Number:	WO96/11914

International Family Members for US Patent RE42462

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0785926		CA 2008 00037	Denmark
European Patent Office	0785926		91487	Luxembourg
European Patent Office	0785926		300361	Netherlands