US Patent 5,319,097: Claim Scope, Expiration, and Patent Landscape for the Crystalline and Spray-Dried Forms

US Patent 5,319,097 protects selected physical forms of a complex indole-benzoyl-sulfonamide compound, not the compound’s basic chemical structure. Claims 1 through 4 cover a crystalline monohydrate identified by infrared and X-ray diffraction characteristics. Claims 5 and 6 cover a spray-drying process that produces a different physical form. Claim 7 covers the compound dissolved in aqueous acetone.

The patent issued on June 7, 1994. Assuming no later patent-term adjustment, terminal disclaimer, reissue, or enforceable continuation patent altered the term, the pre-1995 US patent term was 17 years from issuance. The patent therefore expired on June 7, 2011. The claims no longer provide an enforceable US patent barrier to generic manufacture, formulation, or sale. [1, 2]

What compound does US Patent 5,319,097 protect?

The patent claims a physical form of:

N-[4-[5-(cyclopentyloxycarbonyl)amino-1-methylindol-3-ylmethyl]-3-methoxybenzoyl]-2-methylbenzenesulfonamide.

The patent does not claim the compound solely by its molecular formula or connectivity. Instead, the claims identify particular solid-state and solution forms by:

Hydration state
Crystallinity
Infrared absorption peaks
X-ray powder diffraction peaks
Melting-point range
Degree of freedom from other polymorphs
Manufacturing method
Solvent system

The claim set therefore belongs to the solid-form and process-patent category rather than the core composition-of-matter category.

What is the likely technical purpose of the patent?

The claim language indicates that the inventor identified more than one physical form of the active compound:

Form	Patent treatment	Key identifiers
Crystalline monohydrate	Claims 1-4	IR peaks at 3560, 1690, 1660, 1540, 1440, 1165, 880 and 858 cm⁻¹; XRD peaks at 2θ of 10.0°, 11.2°, 14.6°, 19.8° and 23.0°
Crystalline monohydrate with melting point	Claim 2	Same IR and XRD profile; melting point of 145-155°C
Substantially pure monohydrate	Claims 3-4	Substantially free of other physical or crystalline forms
Spray-dried form	Claims 5-6	IR peaks at 1690, 1530, 1490, 1420, 1155, 1060, 862 and 550 cm⁻¹; melting point of 115-140°C
Aqueous-acetone solution	Claim 7	Compound dissolved in aqueous acetone

The different melting-point ranges strongly suggest that claims 1-4 and claims 5-6 target distinct solid forms. The monohydrate melts at approximately 145-155°C, while the spray-dried form melts at approximately 115-140°C.

What do claims 1 through 4 cover?

Claims 1 through 4 cover the crystalline monohydrate form.

How broad is claim 1?

Claim 1 requires all of the following:

The specified indole-benzoyl-sulfonamide compound.
A monohydrate.
A crystalline form.
The stated infrared peaks.
The stated X-ray powder diffraction peaks.

The claim does not require the absence of other polymorphs. It also does not state a melting point limitation.

The X-ray language requires peaks at 2θ values of 10.0°, 11.2°, 14.6°, 19.8° and 23.0°. Because the claim says the pattern has those peaks, a competing sample could still fall within the claim if it has additional peaks, provided the required peaks are present and the other claim limitations are met.

The term "monohydrate" requires approximately one water molecule per molecule of active compound, subject to the analytical tolerances ordinarily applied to solid-state characterization. A completely anhydrous polymorph should not satisfy this limitation.

How does claim 2 narrow claim 1?

Claim 2 adds a melting-point requirement of 145-155°C. A product must satisfy the claim 1 identity, hydration, crystallinity, IR, and XRD limitations and must also exhibit the specified melting range.

This is a narrower claim and is more vulnerable to analytical variation. Melting point can vary with:

Heating rate
Sample preparation
Residual solvent
Water content
Instrument calibration
Polymorphic contamination
Decomposition before or during melting

For infringement analysis, X-ray diffraction and water-content data would generally carry greater structural significance than melting point alone.

What do claims 3 and 4 add?

Claim 3 requires the monohydrate to be "substantially free of any other physical forms."

Claim 4 requires it to be "substantially free of other crystalline forms."

Claim 4 is narrower in practical effect because it focuses specifically on other crystalline forms. Claim 3 may reach a broader range of unwanted physical forms, potentially including amorphous material, solvates, hydrates, or other solid-state variants, depending on how the specification defines "physical forms."

The principal enforcement issue is the meaning of "substantially free." The patent would need to provide an objective basis for determining the acceptable level of another form. A purity threshold, quantitative XRD method, thermal analysis method, or specification-defined analytical test would strengthen these claims. Without such a benchmark, the phrase may create claim-construction and definiteness disputes under 35 U.S.C. §112. [3]

What do claims 5 and 6 cover?

Claims 5 and 6 cover a spray-drying process that produces a different physical form of the compound.

What limitations are required by claim 5?

Claim 5 requires:

A solution of the specified compound.
Spray drying that solution.
Production of a physical form having the specified IR spectrum.
A melting point between 115°C and 140°C.

The claim is not limited to aqueous acetone. It covers spray drying a solution generally, provided the resulting product has the required analytical characteristics.

Claim 5 is therefore a process claim with a product-characterization limitation. A party that uses spray drying but produces a form outside the stated IR and melting-point parameters may avoid literal infringement of claim 5. Conversely, a party using a different solvent but obtaining the claimed form could still face infringement if the spray-drying and product limitations are met.

How does claim 6 narrow claim 5?

Claim 6 requires the use of an aqueous acetone solution. It is narrower than claim 5 because it adds a solvent-system limitation.

A process using:

Pure acetone,
Water and another organic solvent,
Ethanol-water,
Methanol-water,
A nonaqueous solvent, or
A solvent-free melt

would not literally satisfy the aqueous-acetone limitation of claim 6, although it could still implicate claim 5 if all claim 5 requirements are met.

What does claim 7 cover?

Claim 7 covers a solution of the compound in aqueous acetone. It is a composition or product claim rather than a process claim.

The claim does not specify:

Concentration
Water-to-acetone ratio
Temperature
pH
Container
Intended use
Sterility
Pharmaceutical excipients
Stability period
Spray-drying parameters

That breadth creates potential enforcement reach, but it also creates validity and enablement questions. The claim may cover an intermediate manufacturing solution rather than a final dosage form. A finished tablet, capsule, suspension, or dry powder would not ordinarily fall within claim 7 unless it contains the claimed aqueous-acetone solution.

How do the claims compare?

Claim	Claim category	Key limitation	Relative breadth
1	Product, solid form	Crystalline monohydrate with IR and XRD profile	Broadest monohydrate claim
2	Product, solid form	Claim 1 plus 145-155°C melting point	Narrower
3	Product, solid form	Claim 1 plus substantially free of other physical forms	Narrower purity limitation
4	Product, solid form	Claim 1 plus substantially free of other crystalline forms	Narrower purity limitation
5	Process plus product result	Spray drying; IR profile; 115-140°C melting point	Broad spray-drying process claim
6	Process plus product result	Claim 5 using aqueous acetone	Narrower than claim 5
7	Solution composition	Compound dissolved in aqueous acetone	Broad solution claim, subject to construction

When did US Patent 5,319,097 lose exclusivity?

US Patent 5,319,097 expired on June 7, 2011 under the ordinary 17-year term applicable to patents issued from pre-June 8, 1995 applications. [1, 2]

Event	Date
US patent issuance	June 7, 1994
Ordinary patent term	17 years from issuance
Projected expiration	June 7, 2011
Current enforceability of original claims	Expired

The original patent cannot support a current US infringement action for conduct occurring after expiration. Patent expiration also eliminates the patent’s ability to block an ANDA applicant through a current Paragraph IV dispute.

A separate later patent could still affect commercial entry if it claimed a different polymorph, formulation, dosage regimen, salt, method of use, or manufacturing process. That possibility must be evaluated through the patent family and the relevant FDA Orange Book listing rather than from US 5,319,097 alone.

What is the Orange Book status of US Patent 5,319,097?

The patent’s present Orange Book significance is effectively zero because the patent has expired.

A patent may be relevant to an approved drug only if it is listed for the applicable reference-listed drug and remains unexpired or otherwise enforceable. The claims supplied here are directed to physical forms and manufacturing materials. They are not facially directed to a dosage regimen or therapeutic method of use.

The patent’s expired status means:

It should not support a current 30-month stay under Hatch-Waxman.
It should not create a current Paragraph IV litigation event.
It should not prevent an ANDA applicant from relying on the reference product’s approval.
It should not block use of the claimed monohydrate or spray-dried form solely on the basis of this patent.
It does not eliminate possible barriers from later patents.

Under 21 U.S.C. §355(j), an ANDA applicant may certify that a listed patent has expired or provide a Paragraph IV certification that the patent is invalid, unenforceable, or will not be infringed. An expired patent does not create a live Paragraph IV challenge. [4]

What patent litigation and settlement risk does this patent create?

US Patent 5,319,097 creates no current standalone litigation risk because it expired in 2011.

The historical litigation risk would have been concentrated in three areas:

Solid-form infringement

A generic manufacturer could have faced an infringement claim if its API or drug product contained the crystalline monohydrate satisfying the claimed IR and XRD characteristics.

Process infringement

A manufacturer could have faced a process claim if it used spray drying and produced the claimed form. Claim 6 presented a more specific risk where the manufacturing process used aqueous acetone.

Intermediate-solution use

Claim 7 could have reached manufacturing operations involving the active compound dissolved in aqueous acetone. Its practical value would have depended on whether the claimed solution was used commercially and whether the accused process occurred in the United States.

No current settlement or Paragraph IV exposure can be attributed to this expired patent alone. Any settlement analysis would require a separate review of later patents and the approved-product patent listing.

How strong was the patent estate?

The original patent estate was technically focused but narrow relative to a composition-of-matter patent.

Strengths

It identified a defined crystalline monohydrate.
It used multiple analytical fingerprints: IR, XRD, and melting point.
Claims 3 and 4 attempted to capture high-purity material.
Claims 5 and 6 addressed a manufacturing route that could produce a separate physical form.
Claim 7 covered an aqueous-acetone processing solution.

Weaknesses

The patent did not claim the underlying chemical compound broadly.
The monohydrate claims depend on analytical parameters that require reproducible testing.
"Substantially free" may require specification-based numerical interpretation.
The spray-dried-form claims may be vulnerable to differences in particle history, residual solvent, water content, and thermal analysis.
Claim 7 may face scope, enablement, or indefiniteness disputes because it does not define solvent proportions or concentration.
Expiration eliminates all prospective enforcement value.

The patent was most valuable as a development and manufacturing-control right during its term. It was not a durable barrier comparable to a composition-of-matter patent.

What generic entry risks exist now?

The direct risk from US 5,319,097 is no longer material.

A generic or contract manufacturer can generally pursue:

The claimed monohydrate
A different polymorph
An amorphous form
A solvent-free form
A different hydrate or solvate
A spray-dried form
An alternative drying process
A different solvent system
A different formulation

The relevant remaining risks would come from later patent rights, regulatory exclusivity, trade secrets, or manufacturing know-how. The expired patent itself does not prevent commercial manufacture.

What manufacturing and IP barriers remain relevant?

Although the patent has expired, the claimed characterization methods remain commercially relevant for freedom-to-operate testing.

A manufacturer should distinguish among:

API identity testing.
Hydration-state determination.
Polymorph identification.
Quantification of crystalline contamination.
Residual-solvent analysis.
Spray-drying process validation.
Batch-to-batch solid-state consistency.
Stability under humidity and temperature stress.

The patent’s XRD and IR profiles could still function as technical specifications in development work. They no longer function as enforceable exclusivity rights under the expired patent.

How does this patent compare with a composition-of-matter patent?

Issue	US 5,319,097	Composition-of-matter patent
Protected subject	Specific forms and processes	Chemical compound itself
Typical design-around options	Alternative polymorph, solvent, hydrate, process	Usually limited before expiration
Analytical dependence	High	Lower
Manufacturing relevance	High	Variable
Orange Book durability	Usually limited	Often central
Post-expiration value	Technical reference	Public-domain compound
Generic entry effect	Form-specific during term	Broad market barrier during term

The distinction matters because a manufacturer could potentially avoid an unexpired physical-form patent through a noninfringing polymorph or process. That option would not ordinarily exist against a valid, unexpired composition-of-matter claim covering the active ingredient itself.

Key Takeaways

US Patent 5,319,097 claims physical forms and manufacturing conditions, not the basic chemical structure.
Claims 1-4 cover a crystalline monohydrate identified by IR and XRD characteristics.
Claim 2 adds a 145-155°C melting-point range.
Claims 3 and 4 impose purity limitations relating to other physical or crystalline forms.
Claims 5 and 6 cover spray-drying processes producing a distinct form with a 115-140°C melting point.
Claim 7 covers the compound in aqueous acetone.
The patent issued June 7, 1994 and expired June 7, 2011 under the ordinary pre-1995 patent term.
The patent creates no current US blocking right, Paragraph IV exposure, or 30-month stay.
Any present generic-entry risk must arise from later patents, regulatory exclusivity, or non-patent manufacturing barriers.
The patent remains relevant as a technical reference for polymorph, hydrate, IR, XRD, and spray-drying control.

Frequently Asked Questions

Can a generic manufacturer use the monohydrate claimed in US 5,319,097?

Yes. The patent expired on June 7, 2011, so the expired claims no longer independently prohibit use of the claimed monohydrate in the United States.

Does the patent cover every crystalline form of the compound?

No. Claims 1-4 require a specific monohydrate and defined IR and XRD characteristics. Other crystalline forms fall outside those claims unless they also satisfy the required limitations.

Is spray drying itself patented by US 5,319,097?

No. The patent does not claim spray drying in the abstract. Claims 5 and 6 require spray drying a solution of the specified compound and producing a form with specified analytical characteristics. Claim 6 adds aqueous acetone.

Could a different solvent avoid claim 6?

Potentially, yes. Claim 6 specifically requires an aqueous acetone solution. A different solvent system would not literally satisfy that limitation, although claim 5 could remain relevant if the spray-drying and product-characterization requirements are met.

Does expiration of US 5,319,097 prove that the drug has no remaining patent barriers?

No. Expiration removes the barrier created by this patent. Later patents covering formulations, methods of use, alternative solid forms, salts, delivery systems, or manufacturing processes could have separate expiration dates and separate enforcement rights.

References

United States Patent No. 5,319,097. (1994). Physical forms of N-[4-[5-(cyclopentyloxycarbonyl)amino-1-methylindol-3-ylmethyl]-3-methoxybenzoyl]-2-methylbenzenesulphonamide. United States Patent and Trademark Office.
United States Code, 35 U.S.C. §154. (2023). Contents and term of patent; provisional rights.
United States Code, 35 U.S.C. §112. (2023). Specification.
United States Code, 21 U.S.C. §355(j). (2023). Abbreviated application for new drug.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
United Kingdom	9027014	Dec 12, 1990
United Kingdom	9115107	Jul 12, 1991

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
African Regional IP Organization (ARIPO)	285	⤷ Start Trial
African Regional IP Organization (ARIPO)	9100340	⤷ Start Trial
Austria	131048	⤷ Start Trial
Australia	656157	⤷ Start Trial
Australia	8899491	⤷ Start Trial
Belgium	1004229	⤷ Start Trial
Canada	2056066	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,319,097

Summary for Patent: 5,319,097