Details for Patent: 5,629,425

Summary for Patent: 5,629,425

Title:	Haloalkyl hemisolvates of 6-hydroxy-2-(4-hydroxyphenyl)-3-[4-piperidinoethoxy)-benzoyl]benzo[b]thiophene
Abstract:	The present invention is directed to chemical processes for preparing 2-aryl-6-hydroxy-3-[4-(2-aminoethoxy)benzoyl]benzo[b]thiophenes. The present invention is also directed to crystalline solvates and a non-solvated crystalline form of 6-hydroxy-2-(4-hydroxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo[b]thiophene hydrochloride, as well as processes for their preparation.
Inventor(s):	Elizabeth S. LaBell, John M. McGill, Randal S. Miller
Assignee:	Eli Lilly and Co
Application Number:	US08/308,325
Patent Claim Types: see list of patent claims	Compound;

Scope and claims analysis for US Patent 5,629,425: hemisolvated 6-hydroxy-2-(4-hydroxyphenyl)-3-[4-(piperidinoethoxy)benzoyl]benzo[b]thiophene hydrochlorides

US 5,629,425 is a composition-of-matter patent that is tightly centered on one specific therapeutic core compound, defined as a hydrochloride salt, and on its defined hemisolvate forms with specified solvents (1,2-dichloroethane and 1,2,3-trichloropropane). Claims 1 and 4 set the chemical scope at the solvent-hemisolvate level. Dependent claims 2-3 and 5 provide crystalline form scoping via X-ray diffraction (XRD) pattern requirements, which materially narrow enforceable coverage to the claimed crystalline datasets.

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What is US Patent 5,629,425 and what compound does it cover?

Featured snippet answer: US 5,629,425 claims solvent hemisolvates (1,2-dichloroethane and 1,2,3-trichloropropane) of a specific hydrochloride salt of 6-hydroxy-2-(4-hydroxyphenyl)-3-[4-(piperidinoethoxy)benzoyl]benzo[b]thiophene.

Core active molecule in the claims

The structural identity in claims 1 and 4 is consistent across both hemisolvate families:

• Compound backbone: 6-hydroxy-2-(4-hydroxyphenyl)-3-[4-(piperidinoethoxy)benzoyl]benzo[b]thiophene
• Salt state: hydrochloride
• Solvent inclusion form: hemisolvate with a specified chlorinated solvent

So the enforceable object is not the general hydrochloride salt per se, but rather the defined hemisolvate crystal forms of that hydrochloride.

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What do claim 1 and claim 4 cover in US 5,629,425?

Featured snippet answer: Claim 1 covers the 1,2-dichloroethane hemisolvate of the specified hydrochloride; claim 4 covers the 1,2,3-trichloropropane hemisolvate.

Claim 1

“1,2-dichloroethane hemisolvate of 6-hydroxy-2-(4-hydroxyphenyl)-3-[4-(piperidinoethoxy)benzoyl]benzo[b]thiophene hydrochloride.”

Scope implications

• Covers compositions where the active exists as a hemisolvate with 1,2-dichloroethane.
• Drafting is compound-form-specific: if a competitor makes the hydrochloride salt without 1,2-dichloroethane hemisolvate, claim 1 is unlikely to read.
• If a competitor produces other solvates (e.g., other halo-organics, alcohols) or anhydrate/polymorphs without that solvent stoichiometry, claim 1 generally does not capture those products.

Claim 4

“1,2,3-trichloropropane hemisolvate of 6-hydroxy-2-(4-hydroxyphenyl)-3-[4-(piperidinoethoxy)benzoyl]benzo[b]thiophene hydrochloride.”

Scope implications

• Mirrors claim 1 but with a different included solvent.
• The second solvent changes the identity of the “hemisolvate” phase being claimed, so the two claim families act as separate “form” hooks.

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How do dependent claims 2–3 narrow scope using XRD patterns?

Featured snippet answer: Claims 2 and 3 restrict coverage to crystalline 1,2-dichloroethane hemisolvate forms that match specific copper-radiation XRD line-spacing datasets.

Claim 2 dataset (1,2-dichloroethane hemisolvate crystalline form)

Claim 2 requires the crystalline 1,2-dichloroethane hemisolvate to have an XRD pattern with the listed d-spacings and relative intensities (I/I₀ ×100).

Key enforcement-relevant structure:

• The claim is not “broad crystalline.” It is pattern-defined.
• If an accused product’s XRD has systematic shifts, missing peaks, or different relative intensity ranking, the claim can become difficult to satisfy depending on infringement doctrine applied (not provided in the record here).

Representative d-spacings in claim 2 include:

• 10.4311 (22.64)
• 8.9173 (10.73)
• 8.4765 (5.31)
• 8.0095 (50.39)
• 7.3068 (4.23)
• 6.6094 (79.23)
• 5.6196 (22.34)
• 5.4223 (89.86)
• 5.1959 (11.81)
• 5.0746 (74.90)
• 4.8017 (100.00)
• 4.6569 (53.35)
• 4.5378 (96.75)
• 4.3397 (56.89)
• 4.2782 (48.23)
• 4.2129 (40.94)
• 4.1037 (12.80)
• 3.9880 (14.76)
• 3.7999 (42.13)
• 3.6738 (38.58)
• 3.5393 (19.00)
• 3.3867 (5.02)
• 3.2686 (6.79)
• 3.1535 (14.86)
• 3.0450 (13.58)
• 2.9028 (12.30)
• 2.8302 (19.59)
• 2.7544 (12.30)
• 2.6366 (6.89)

Scope implications

• Claim 2 acts as a “crystal-form lock,” capturing a particular diffraction signature of the dichloroethane hemisolvate.
• In practice, this creates two risk paths for competitors:
  1. They must match the exact crystalline phase.
  2. They must do so with the same measurement conditions (claimed Cu radiation is specified in the claim text you provided).

Claim 3 dataset (another crystalline form for the same solvent hemisolvate)

Claim 3 is again a crystalline 1,2-dichloroethane hemisolvate, but with a different XRD dataset than claim 2. That indicates the patent differentiates at least two crystallographic forms for the same solvent inclusion type.

Representative d-spacings in claim 3 include:

• 16.1265 (3.80)
• 10.3744 (8.63)
• 8.3746 (5.29)
• 7.9883 (36.71)
• 7.2701 (5.06)
• 6.5567 (70.77)
• 5.5616 (24.05)
• 5.3879 (100.00)
• 5.0471 (89.64)
• 4.7391 (85.96)
• 4.6777 (39.36)
• 4.6332 (62.60)
• 4.5191 (77.56)
• 4.2867 (36.82)
• 4.2365 (41.66)
• 4.1816 (49.60)
• 4.0900 (11.28)
• 3.9496 (11.85)
• 3.7869 (36.25)
• 3.7577 (56.16)
• 3.6509 (40.62)
• 3.5751 (15.65)
• 3.5181 (21.52)
• 3.4964 (18.53)
• 3.4361 (33.60)
• 3.3610 (6.21)
• 3.3115 (4.95)
• 3.2564 (7.36)
• 3.2002 (3.80)
• 3.1199 (15.77)
• 3.0347 (14.84)
• 2.8744 (9.67)
• 2.8174 (10.82)
• 2.7363 (11.51)

Scope implications

• Dependent claims 2 and 3 likely correspond to two distinct polymorphs of the dichloroethane hemisolvate.
• This increases coverage: a generic attempting to use the dichloroethane hemisolvate crystalline material must hit at least one of these defined patterns to fall within the dependent claims.

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How do claim 5 and claim 4 relate (XRD narrowing for the trichloropropane hemisolvate)?

Featured snippet answer: Claim 5 restricts the 1,2,3-trichloropropane hemisolvate to a specific crystalline XRD pattern (Cu radiation), using the listed d-spacings and relative intensities.

Claim 5 dataset

Claim 5’s XRD list you provided is identical to the list shown in claim 2 in your excerpt (the long dataset that begins at 10.4311 22.64 and includes 4.8017 100.00 and 4.5378 96.75 and ends at 2.6366 6.89).

Scope implications

• The same XRD dataset being used in claim 5 suggests either:
  • the patent drafters treated the crystalline pattern as shared across these hemisolvate solvates, or
  • a transcription overlap exists in the text you supplied (cannot be corrected here).
• Legally, as written, claim 5 requires both the solvent identity (1,2,3-trichloropropane hemisolvate) and the specific diffraction signature.

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What is the practical patent landscape effect of solvent-hemisolvate claim strategy?

Featured snippet answer: The patent is structured as a solvent-form IP barrier. It can be difficult to design around because competitors must control both (a) included solvent identity and (b) crystallinity/polymorph, not just salt formation.

Design-around pathways suggested by the claim scope

Given only these claims, a product is outside coverage if it:

• uses a different solvate/hemisolvate solvent inclusion (no 1,2-dichloroethane or no 1,2,3-trichloropropane hemisolvate),
• uses a different hydrate/anhydrate state that does not qualify as a hemisolvate,
• produces a different crystalline form that does not match the listed XRD datasets for the dichloroethane hemisolvate (dependent claims 2–3) or trichloropropane hemisolvate (claim 5),
• avoids the hydrochloride salt state.

This matters for generic and lifecycle strategy because many manufacturing routes start from salts and may create solvates unintentionally. The claim language ties directly to those outcomes.

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How many distinct protected “forms” does the patent create?

Featured snippet answer: At least three crystalline form claims exist across the solvent-hemisolvate families as presented: claim 1 (dichloroethane hemisolvate, non-crystal constrained), claim 2 and claim 3 (two XRD-defined crystalline dichloroethane hemisolvate forms), and claim 4 and claim 5 (trichloropropane hemisolvate with XRD constraint).

Form inventory by claim

Claim	Solvate / form	Crystal requirement	XRD dataset requirement provided
1	1,2-dichloroethane hemisolvate of specified HCl salt	Not specified in claim text provided	No
2	Crystalline 1,2-dichloroethane hemisolvate	Yes	Yes (Cu radiation list A)
3	Crystalline 1,2-dichloroethane hemisolvate	Yes	Yes (Cu radiation list B)
4	1,2,3-trichloropropane hemisolvate of specified HCl salt	Not specified in claim text provided	No
5	Crystalline 1,2,3-trichloropropane hemisolvate	Yes	Yes (Cu radiation list as provided)

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What does the claim drafting imply about scope strength for enforcement?

Featured snippet answer: The patent has a medium-to-strong enforcement profile against products that contain the specific solvent hemisolvates, with additional strength for crystalline forms that match the XRD datasets.

Where the patent is strong

• Direct solvent identification: claim 1 and claim 4 are tied to named solvents and hemisolvate stoichiometry (conceptually).
• Crystalline fingerprinting: dependent claims 2, 3, and 5 use Cu radiation XRD d-spacing/intensity tables, which can be used as a testing comparator in litigation.

Where the patent is narrower than typical salt-only coverage

• It does not, as presented, claim “all crystalline forms” of the hydrochloride salt.
• It does not, as presented, claim other solvates.
• It requires specific hemisolvate solvent identity and (for dependent claims) specific crystallinity signatures.

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How would an ANDA Paragraph IV strategy likely be evaluated against these claims?

Featured snippet answer: Risk hinges on whether the ANDA product manufacturing yields the same solvent hemisolvate and, if crystalline forms are asserted, whether the submitted solid-state characterization matches the claimed XRD datasets.

Factual infringement checkpoints

• Solid-state characterization:
  • Identify whether the ANDA bulk is a 1,2-dichloroethane hemisolvate or 1,2,3-trichloropropane hemisolvate.
• If the product is the correct hemisolvate:
  • Determine whether it matches the XRD dataset in claim 2 or claim 3 for dichloroethane hemisolvate, and claim 5 for trichloropropane hemisolvate.

Typical risk ranking implied by the claim set

1. Products intentionally produced to match claim 1 or claim 4 are highest risk.
2. Products that inadvertently form those hemisolvates during crystallization are still risk-bearing if the resulting phase matches.
3. Products that use different solvates or amorphous/anhydrous forms are lower risk if they avoid claim identity.

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What is the Orange Book status of US 5,629,425 and when does it expire?

No answer provided. The required Orange Book listing status, FDA application linkage, and USPTO expiration timeline are not supplied in the prompt, and cannot be derived reliably from claim text alone.

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Key Takeaways

• US 5,629,425 claims a specific hydrochloride salt of 6-hydroxy-2-(4-hydroxyphenyl)-3-[4-(piperidinoethoxy)benzoyl]benzo[b]thiophene in hemisolvate forms.
• Claim 1 and claim 4 define two solvent hemisolvates: 1,2-dichloroethane and 1,2,3-trichloropropane.
• Claims 2 and 3 add two distinct XRD-defined crystalline forms for the 1,2-dichloroethane hemisolvate, using Cu radiation d-spacing and relative intensity tables.
• Claim 5 adds an XRD fingerprint for the crystalline 1,2,3-trichloropropane hemisolvate.
• Enforceable scope is strongest for products that match both solvent hemisolvate identity and, where asserted, the exact crystalline XRD dataset.

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FAQs

1) Does US 5,629,425 cover the hydrochloride salt without included solvent?
No based on the provided claim language, which requires hemisolvate forms (claims 1 and 4) and crystalline hemisolvate forms with XRD datasets (claims 2–3 and 5).

2) Can a competitor design around by using a different solvate solvent?
A different solvate generally falls outside claim 1/4 because the hemisolvate solvent is expressly limited to 1,2-dichloroethane or 1,2,3-trichloropropane.

3) How many XRD-defined crystalline forms for the dichloroethane hemisolvate are claimed?
Two, represented by claims 2 and 3, each with its own Cu-radiation XRD d-spacing/intensity table.

4) If a product matches claim 1, does it automatically infringe claims 2 or 3?
Not automatically. Claim 1 does not impose the XRD dataset restriction, while claims 2 and 3 require specific crystalline XRD patterns.

5) What tests are most relevant to proving infringement for claims 2, 3, and 5?
Solid-state characterization by XRD under conditions consistent with the claim requirement (Cu radiation, and the cited d-spacing and intensity list).

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References

1. United States Patent 5,629,425 (claims as provided in prompt).

Drugs Protected by US Patent 5,629,425

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 5,629,425

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
African Regional IP Organization (ARIPO)	754
African Regional IP Organization (ARIPO)	9700938
Austria	407988
Austria	502957
Austria	504859
Austria	A154295
Australia	3173095