Details for Patent: 5,710,285

Summary for Patent: 5,710,285

Title:	Process for preparing 2-substituted benzo B!thiophene compounds and intermediates thereof
Abstract:	The present invention provides useful intermediates for preparing 2-(substituted phenyl)benzothiophenes compounds said intermediates having the structure ##STR1## wherein R1 ' is --OH, or --OR3, in which R3 is a hydroxy protecting group; andZ is bromo, iodo, triflate, or --B(OH)2 with the proviso that when Z is bromo or iodo, R1' is not alkoxy.
Inventor(s):	Kenneth L. Hauser, Alan D. Palkowitz, Daniel J. Sall, Kenneth J. Thrasher
Assignee:	Eli Lilly and Co
Application Number:	US08/549,595
Patent Claim Types: see list of patent claims	Compound;

United States Patent 5,710,285 Scope, Claims Breakdown, and U.S. Patent Landscape

Executive summary U.S. Patent 5,710,285 is an early-process synthetic patent centered on “compound of formula IX” intermediates with variable functionalization at Z (bromo, iodo, triflate, or boronic acid equivalent, i.e., B(OH)2). Claim 1 is the core breadth driver, tying a protected hydroxy substituent (R1 = OH or OR3, where R3 is a hydroxy protecting group) to a halogen/activated leaving group/boronic acid handle at Z, with a single negative limitation that excludes bromo/iodo when R1 is alkoxy (R1′ not alkoxy). Claims 2–8 then narrow by fixing R1 to alkoxy, selecting R3 (C1–C4 alkyl, methyl), and selecting specific Z embodiments (bromo, iodo, or B(OH)2). This is the kind of claim set that typically creates enforceable coverage against use of specific protected intermediate structures as coupling partners, particularly where the claimed Z substituent enables Suzuki or related cross-coupling.

Because the record you provided contains only the claim text and no drug name, active ingredient identity, assignee, priority data, related families, or prosecution history, the analysis below focuses on claim scope mechanics and an enforceable “landscape map” of what the claim language is designed to cover in practice: protected intermediate classes, functional handle interchange, and likely non-infringing design-arounds via swapping Z or deprotecting R1 under the proviso.

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What does US 5,710,285 claim for “compound of formula IX”?

Featured snippet (scope answer) Claim 1 covers compounds of formula IX where:

• R1 is either hydroxy (OH) or an alkoxy ether (OR3), with R3 being a hydroxy protecting group
• Z is one of: bromo, iodo, triflate, or B(OH)2
• If Z is bromo or iodo, R1′ (the claim’s designated R1 substituent in that situation) is not alkoxy (i.e., the OR3 form is excluded under halogen embodiments)

That combination creates a claim structure that is broad on Z (multiple leaving-group or coupling-handle options) and moderately broad on protection chemistry (any R3 that qualifies as a hydroxy protecting group), but narrows the specific overlap between halogen Z and alkoxy R1.

How to read the claim variables (R1 vs R3 vs Z)

• R1: two “states” are allowed in Claim 1
  • R1 = --OH
  • R1 = --OR3 where R3 is a hydroxy protecting group
• R3: a protecting group on the oxygen. The claim does not limit to a specific set in Claim 1, but dependent claims narrow to C1–C4 alkyl and then methyl.
• Z: a functional handle installed on the core scaffold. It is explicitly one of four options:
  • bromo (–Br)
  • iodo (–I)
  • triflate (–OTf)
  • B(OH)2 (boronic acid)

The key legal limiter: the proviso for bromo/iodo

Claim 1 contains a “with proviso” clause that is central to scope:

• If Z is bromo or iodo, then R1′ is not alkoxy.

In practical terms, the proviso prevents claim coverage for the specific intersection:

• Z = Br or I
• R1 = OR3 (alkoxy) rather than OH

So, under Claim 1:

• Z = Br/I can be covered only when R1 is OH (not OR3).
• Z = triflate or B(OH)2 can be covered with either R1 = OH or R1 = OR3 (subject to dependent claim narrowing where applicable).

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Which dependent claims narrow scope and how do they change infringement risk?

Claim 2: R1 is alkoxy (OR3)

Claim 2 states: “A compound according to claim 1 wherein R1′ is --OR3.”

Impact: Claim 2 limits Claim 1 to the protected (ether) state of the hydroxy group. That matters because Claim 1’s proviso restricts the OR3 state only when Z is Br or I. Therefore:

• Under Claim 2, Z cannot be bromo or iodo, because Claim 1 requires “not alkoxy” when Z is Br/I.
• Claim 2 therefore implicitly pushes covered embodiments toward:
  • Z = triflate, and/or
  • Z = B(OH)2, while still allowing Z = Br/I only if the proviso can be reconciled (but the proviso’s wording is a direct conflict with “R1′ is --OR3” when Z is Br/I).

Claim 3: R3 is C1–C4 alkyl

Claim 3 narrows the protecting group class to small alkyl ethers.

Impact: This is a major practical narrowing. If a competitor uses a different protecting group (benzyl, silyl, acyl-type, etc.), Claim 3 is avoided. If they use an alkyl ether within C1–C4 (methyl, ethyl, propyl, isopropyl, butyl variants), they can fall into this dependent claim.

Claim 4: R3 is methyl

Claim 4 fixes the protecting group to methyl.

Impact: This is the narrowest protection selection. It is easier to design around by using:

• other alkyl groups (ethyl, propyl),
• non-alkyl protecting groups (silyl ether such as TBDMS/TMS),
• acyl protecting groups (if chemically consistent with “R3 is a hydroxy protecting group” in the formula).

However, Claim 1 is broader than Claim 4, so design-around is less about “avoid methyl” and more about “avoid the entire claimed intersection of R1 state and Z substitution.”

Claim 5: R3 is methyl and Z is B(OH)2

Claim 5 selects the combination:

• R3 = methyl
• Z = B(OH)2

Impact: This is a very specific intermediate structure: a methyl-protected oxygenated scaffold bearing a boronic acid handle. It can capture specific synthetic routes where a boronic acid intermediate is isolated with methyl protection.

Claims 6–8: specific Z embodiments

• Claim 6: Z = bromo (and base Claim 1 applies)
• Claim 7: Z = iodo (and base Claim 1 applies)
• Claim 8: Z = B(OH)2 (and base Claim 1 applies)

Impact by proviso:

• Claims 6 and 7 must reconcile with the Claim 1 proviso. Because Z is Br/I, Claim 1 requires R1′ is not alkoxy. So these dependent claims cover Br/I intermediates that have R1 = OH (unprotected hydroxy), not OR3.
• Claim 8 covers B(OH)2 intermediates without the Br/I proviso restriction. R1 can be OH or OR3 (subject to any other dependent narrowing not present in Claim 8).

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What “functional handle” does Z represent, and how does that drive typical coupling use?

Even without the drawn structure of formula IX, the variable Z set strongly implies that the scaffold can be advanced via cross-coupling:

• B(OH)2 is characteristic of Suzuki coupling partners
• bromo/iodo are typical electrophile handles for Suzuki and related couplings
• triflate is an activated electrophile handle often used for Pd-catalyzed substitutions and couplings

Business relevance: If a synthesis uses one of these intermediates as a coupling partner, the claim set can be asserted against:

• the intermediate itself (product coverage),
• manufacturing routes that result in these specific protected/unprotected Z forms,
• and, depending on the jurisdiction and posture, the “use” of those intermediates in preparation of drug substances.

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How does the proviso alter design-around options?

Non-infringing strategies implied by the language

Given the explicit proviso, competitors have three straightforward structural levers:

1. Keep Z = Br or I but protect hydroxy with OR3

   • This is the direct conflict: Claim 1 says Z = Br/I and R1′ is not alkoxy.
   • If the competitor uses an alkoxy-protected oxygen while keeping Br or I at Z, they aim at escaping Claim 1 coverage under the proviso.

2. Switch Z away from the claimed set

   • Avoid Z ∈ {bromo, iodo, triflate, B(OH)2}.
   • Replace Z with another electrophile or masked boron form not captured by the literal wording (e.g., different boron ester that is not B(OH)2).
   • This is a classic workaround because dependent claims do not broaden Z beyond Claim 1.

3. Avoid the claimed R3 scope

   • For dependent claims (3 and 4), use a protecting group that is not C1–C4 alkyl or not methyl.
   • Note: This does not necessarily avoid Claim 1, because Claim 1 broadly accepts any hydroxy protecting group; it only helps avoid dependent claim coverage.

What is the likely litigation focal point

Most disputes will concentrate on:

• whether a compound has Z exactly as bromo/iodo/triflate/boronic acid equivalent (literal identity),
• whether the hydroxy substituent is R1 = OH or R1 = OR3 (chemically protected),
• and how the proviso is construed for overlap between “R1′” wording and “R1” in claim drafting.

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U.S. patent landscape: how does 5,710,285 typically sit in a synthetic family?

With only the claim text, a complete competitor landscape cannot be enumerated accurately without:

• patent title and assignee,
• priority data,
• the publication number and application number,
• the full specification including the definition of “formula IX,”
• and the family members (continuations, divisionals, and foreign equivalents).

Still, the claim mechanics let an investor or litigator infer the landscape structure that commonly surrounds a patent like this:

Common adjacent patent layers in such estates

1. Core scaffold intermediate patents
   • Claims like “compound of formula IX” often cover early or late-stage intermediates rather than final drug substances.
2. Protection-group variants
   • Dependent claims narrowing to C1–C4 alkyl and methyl protection suggest parallel claims may exist covering other protecting groups in related families.
3. Z handle variant patents
   • By including multiple Z options (Br/I/triflate/B(OH)2), the claim set tries to prevent simple “one-letter” substitutions in coupling handle selection.
4. Downstream coupling or transformation patents
   • Patents that claim the next steps after installing the Z handle: cross-coupling products, further functionalization, and ultimately active pharmaceutical ingredient formation.

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What patent strength does this claim set have (scope breadth vs. specificity)?

Strength indicators

• Claim 1 breadth on Z: four handle types are covered.
• Claim 1 includes protected and unprotected R1 states: it covers both OH and OR3, except for the Br/I proviso intersection.
• Dependent claims tightly ladder to specific intermediates: they create multiple fall-back positions for enforcement.

Vulnerabilities

• Z is tightly enumerated: if a competitor uses a different activation handle or boron form not literally B(OH)2, they can avoid the literal claim.
• The proviso is a carve-out: it narrows the claim’s ability to cover Br/I with alkoxy-protected hydroxy forms.
• Dependent claim narrowing may create “gaps”: if competitors use non-C1–C4 protecting groups or non-methyl protection, dependent claims 3–5 become less useful, leaving Claim 1 as the main anchor.

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How many patents would likely cover the same chemistry in the U.S.?

Without the patent bibliographic record and family list, a numeric count cannot be stated from the provided inputs without fabricating data. What can be stated from the claim architecture is the likelihood of multiple U.S. filings typical to such chemical estates:

• at least one claim set covering the scaffold with varied Z,
• at least one set addressing protection group permutations,
• and likely continuations to secure additional fallback positions.

But a quantified count would be speculative without the patent record.

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What commercial/IP barriers does this patent likely create?

For process development

If a CDMO or internal process uses intermediates matching formula IX with one of the Z handles and appropriate R1 protection status, this patent can:

• require licensing,
• or prompt redesign of intermediate selection and protection strategy.

For suppliers of coupling intermediates

Any supplier selling or synthesizing the claimed intermediates can face:

• product-based infringement exposure,
• and heightened risk if the intermediates are used as coupling components in generic or analog programs.

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Key takeaways

• Claim 1 is the core coverage: formula IX with R1 = OH or OR3 (any hydroxy protecting group), and Z = Br, I, triflate, or B(OH)2, with a specific proviso excluding OR3 (alkoxy) when Z = Br or I.
• Claims 2–5 narrow the R1 protection state and protecting group identity: they funnel coverage toward ether-protected R1 and, in dependent claims, toward C1–C4 alkyl and methyl protection.
• Claims 6–8 narrow Z by embodiment: bromo and iodo coverage is constrained by the proviso to unprotected hydroxy (R1 = OH), while B(OH)2 coverage remains compatible with protected or unprotected hydroxy under Claim 1.
• Design-arounds implied by the text are structural: alter Z outside the enumerated set, keep Z = Br/I but use OR3 protection to trigger the proviso conflict, or change the protecting group away from C1–C4 (for dependent claims).
• Landscape mapping requires bibliographic data to quantify competing estates, assignations, continuations, and related family members; the provided inputs support only claim-logic and enforceability-by-structure analysis.

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FAQs

1) Does US 5,710,285 cover both boronic acids and boronic acid equivalents?

It explicitly names B(OH)2 in the claim set; scope beyond literal B(OH)2 depends on how the court construes the claim terms and whether the specification defines equivalents, which is not provided here.

2) Can a compound with Z = bromo still infringe if the hydroxy is protected as an ether?

Claim 1’s proviso bars the “alkoxy” (OR3) state when Z is bromo or iodo, so such a compound targets non-infringement on the face of the claim language.

3) If a synthesis uses a methyl-protected intermediate with Z = triflate, which claims are implicated?

Claim 1 would be a candidate if the structure matches formula IX with R1 = OR3 (methyl qualifies) and Z = triflate; Claim 2 and Claim 3/4 may apply depending on the exact protection definition, with Claim 4 specifically requiring methyl.

4) Which claim is most useful for enforcement against boronic acid intermediates?

Claim 8, combined with Claim 1, is directly aimed at Z = B(OH)2; Claims 5 narrows further to methyl protection plus B(OH)2.

5) Does the patent likely cover final API manufacturing or only intermediates?

These claims are structured as “compound of formula IX,” which is characteristic of intermediate coverage, but final coverage cannot be concluded without the specification and how formula IX maps onto the API synthetic sequence.

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References (APA)

No external sources were provided or cited.

Drugs Protected by US Patent 5,710,285

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 5,710,285

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	5326196
Australia	699368
Brazil	9607934
Canada	2216100
China	1073107
China	1180353