United States Drug Patent 6,110,940: Eletriptan Hydrobromide Alpha Polymorph, Claim Scope and Patent Landscape

US Patent No. 6,110,940 protects the alpha-polymorphic form of eletriptan hydrobromide, the active pharmaceutical ingredient in Relpax. The patent does not claim the fundamental eletriptan molecule. Its principal protection is directed to a defined crystalline solid form, analytical fingerprints for that form, pharmaceutical compositions containing it, therapeutic use, and manufacturing processes that convert other forms or intermediates into the alpha polymorph.

The patent was assigned to Pfizer and is expired. Its commercial relevance was strongest before generic eletriptan entry because the alpha form and the process claims could complicate substitution with a different polymorph or a non-infringing manufacturing route.

What drug and crystalline form does US 6,110,940 protect?

US 6,110,940 protects the alpha-polymorphic form of eletriptan hydrobromide, a selective serotonin 5-HT1B/1D receptor agonist used primarily for acute migraine treatment.

Item	Patent subject
Patent	US 6,110,940
Drug	Eletriptan hydrobromide
Brand	Relpax
Patent holder	Pfizer-related entities
Technology	Alpha polymorph of eletriptan hydrobromide
Main dosage form	Oral tablets
Therapeutic category	Triptan antimigraine agent
Priority date	December 19, 1997
US filing date	December 18, 1998
Grant date	August 29, 2000
Expected patent expiration	December 19, 2017
Current status	Expired

The patent’s formula appears in the original patent drawings. The compound identified by the claims is eletriptan hydrobromide, rather than a new chemical entity distinct from eletriptan.

Eletriptan is a small-molecule drug. The relevant regulatory pathway is an abbreviated new drug application, or ANDA, not a biosimilar application under the Public Health Service Act.

What are the principal claims of US 6,110,940?

The claims fall into five groups:

The alpha polymorph itself.
Analytical definitions using infrared spectroscopy and powder X-ray diffraction.
Pharmaceutical compositions.
Methods of treating specified conditions.
Processes for producing the alpha polymorph.

Claims 1 through 3 define the product. Claims 4 through 7 and 11 through 14 define compositions and medical uses. Claims 8 through 10 define manufacturing processes and analytical confirmation of the resulting solid forms.

Claim 1: alpha polymorphic eletriptan hydrobromide

Claim 1 broadly covers the alpha-polymorphic form of the compound of formula (I). It is the core product claim.

The claim is broader than the later analytical claims because it does not expressly require the listed infrared bands or X-ray peaks. In an infringement dispute, the central issue would be whether the accused material is the claimed alpha polymorph, regardless of whether the accused product label identifies that form.

Claims 2 and 3: infrared and X-ray identification

Claim 2 narrows the alpha polymorph by requiring a specified infrared spectrum in a Nujol mull. The spectrum includes characteristic bands at 3371, 3293, 2713, 2524, 1419, 1343, 1307, 1264, 1151, 1086, 1020, 1008, 999, 922, 900, 805, 758, 740, 728, 689, 672, 652, 640, 598, 581, 573, 531, 498, 465, 457, 443, 428, 422, 414 and 399 cm-1.

Claim 3 adds a powder X-ray diffraction requirement. The listed principal reflections are:

Alpha-form XRPD peak, degrees 2θ
9.7
10.7
15.9
16.5
17.8
18.3
19.3
19.8
20.1
21.2
24.4
25.5
25.8
26.7
27.6
29.4

These claims create an analytical boundary between the alpha polymorph and the beta polymorph. The X-ray pattern is likely to carry greater practical weight than the infrared spectrum in solid-form identification because XRPD is commonly used for polymorph characterization and batch release.

A product can infringe a product claim even if its commercial specification uses a different name for the solid form. Conversely, a material that does not exhibit the claimed alpha-form pattern may avoid claims 2 and 3, subject to the scope of claim 1 and any applicable doctrine of equivalents.

What polymorph manufacturing processes are protected?

Claim 8 covers three alternative routes for preparing the alpha polymorph.

Route A: hydrogen bromide treatment and crystallization

The process begins with a solution of formula (II), treats it with aqueous hydrogen bromide, isolates a crude oil, and crystallizes the material from a second solvent.

Claim 9 narrows this route to:

Acetone as the first solvent.
49% w/w aqueous hydrogen bromide.
Treatment at 20°C to 25°C.
2-Propanol as the second solvent.

Route B: conversion of the beta polymorph

The beta polymorph is crystallized from a suitable solvent and the resulting mixture is slurried. The claim therefore reaches a polymorph-conversion process rather than only direct crystallization from an intermediate.

Claim 9 specifies aqueous acetone as the suitable solvent.

Route C: low-temperature hydrogen bromide treatment and slurrying

A solution of formula (II) is treated with aqueous hydrogen bromide, followed by slurrying. The process may include refluxing, cooling and further slurrying.

Claim 9 narrows this route to:

Acetone as solvent.
62% w/w aqueous hydrogen bromide.
Treatment at 0°C to 5°C.

Claim 10 adds XRPD requirements for both polymorphs. The beta form is characterized by principal reflections at 11.0, 17.2, 19.2, 20.1, 21.6, 22.6, 23.6 and 24.8 degrees 2θ.

The process claims are narrower than the product claims because they require particular operations, solvents, reagent concentrations or temperatures. A generic manufacturer could potentially avoid literal infringement by using a different salt-formation route, solvent system, crystallization sequence or temperature profile, although the resulting product would still need to be assessed against the alpha-polymorph claims.

What medical uses are covered by the patent?

Claims 4 through 7 and 11 through 14 cover pharmaceutical compositions and methods using the claimed compound or alpha polymorph.

The listed conditions include:

Migraine.
Cluster headache.
Chronic paroxysmal hemicrania.
Headache associated with a vascular disorder.
Depression.
Anxiety.
Eating disorders.
Obesity.
Drug abuse.
Hypertension.
Emesis.

The practical commercial use is migraine treatment. The broader list reflects the pharmacological class of selective 5-HT1 receptor agonists and does not mean that Relpax was approved for every listed condition.

The claims use open-ended pharmaceutical composition language, requiring an effective amount and a pharmaceutically acceptable carrier. They do not specify a tablet strength, excipient, release profile or particular dosage regimen.

What is the FDA regulatory and Orange Book status?

Relpax was approved by the FDA as eletriptan hydrobromide tablets for the acute treatment of migraine attacks, with 20 mg and 40 mg strengths. FDA labeling identifies eletriptan hydrobromide as the active ingredient and specifies oral administration.

The patent landscape for Relpax included the underlying eletriptan compound patent and the later polymorph patent. The Orange Book listed patent information for Relpax during the branded product’s exclusivity period. US 6,110,940 was a solid-form patent rather than a new chemical entity patent.

Regulatory issue	Assessment
FDA product	Relpax tablets
NDA holder	Pfizer
Active ingredient	Eletriptan hydrobromide
FDA pathway for generics	ANDA
Biosimilar pathway	Not applicable
Orange Book relevance	Listed drug patent and exclusivity framework
Current patent barrier	None from US 6,110,940 because the patent expired

Patent expiration did not terminate FDA approval or prevent continued sale of Relpax. It removed the enforceable patent exclusion associated with this patent.

When did eletriptan lose patent exclusivity?

The fundamental eletriptan compound patent expired before US 6,110,940. The polymorph patent had the later practical expiration date.

Patent layer	Subject matter	Approximate expiration
Core eletriptan patent, including US 5,545,644	Eletriptan compound and therapeutic use	2016
US 6,110,940	Alpha polymorph, analytical definition and process	December 19, 2017
Regulatory exclusivity	NDA-related exclusivity	Expired before the current period

The exact commercial launch date for each generic depended on ANDA approval, Paragraph IV litigation, settlements and any pediatric exclusivity adjustment. Once the relevant patent and exclusivity periods ended, generic manufacturers could commercialize eletriptan tablets subject to FDA approval.

Which companies challenged the Relpax patent estate?

Generic companies typically challenge branded small-molecule patents through Paragraph IV certifications. A Paragraph IV certification states that a listed patent is invalid, unenforceable or will not be infringed by the proposed generic product.

Relpax generated generic competition from companies seeking approval for eletriptan hydrobromide tablets. Public patent records and FDA generic-drug activity identify the competitive field as including major generic manufacturers such as Teva, Mylan and Apotex-related entities, depending on the specific ANDA and litigation record.

The principal legal questions in a Paragraph IV dispute involving US 6,110,940 would have been:

Whether the ANDA product contained the alpha polymorph.
Whether the generic process used one of the claimed crystallization routes.
Whether the analytical limitations were met.
Whether the claims were anticipated or obvious in view of the beta form and prior crystallization methods.
Whether the patent was enforceable and properly listed.

Because US 6,110,940 has expired, any prior Paragraph IV dispute is historical. It no longer creates an injunction risk for current US generic manufacture or sale.

How strong was the patent estate for eletriptan?

The estate was strongest when viewed as a layered structure:

Protection layer	Commercial function	Relative strength during term
Core compound patent	Blocked eletriptan generally	High
Alpha-polymorph patent	Blocked or complicated use of the commercial solid form	Moderate to high
Process claims	Protected specified HBr and crystallization routes	Moderate
Method-of-use claims	Covered listed 5-HT1 indications	Moderate
Formulation claims	Limited unless separately claimed in related patents	Limited under US 6,110,940

US 6,110,940 did not provide comprehensive formulation protection. It does not claim a specific tablet architecture, coating, dissolution profile, excipient combination or controlled-release system. It also does not claim every possible process for producing eletriptan hydrobromide.

Its value depended on the relationship between product claims and process claims. A generic manufacturer that used the alpha polymorph could face product-claim risk. A manufacturer that used another polymorph could avoid some claims but would need to demonstrate that the commercial material was not the claimed alpha form and that its manufacturing route did not fall within claims 8 through 10.

What generic entry risks existed?

Before expiration, the principal generic risks were:

Paragraph IV litigation triggered by an ANDA.
A 30-month stay under the Hatch-Waxman framework after timely litigation.
Difficulty proving that a commercial batch did not contain the patented alpha polymorph.
Infringement allegations based on the manufacturing process rather than the product label.
Analytical disputes over XRPD peak intensity, peak position and acceptable experimental variation.
Potential product-by-process issues if the accused solid form was indistinguishable from the claimed alpha polymorph.

After expiration, those risks became commercial rather than patent-based. Generic competition could target the same strengths and indication, subject to FDA approval, bioequivalence and labeling requirements.

How does US 6,110,940 compare with the core eletriptan patent?

The core patent protected the chemical entity and provided the primary exclusivity period. US 6,110,940 was a later solid-form patent with a narrower but potentially useful extension of market protection.

Characteristic	Core eletriptan patent	US 6,110,940
Protected subject	Eletriptan molecule and related uses	Alpha polymorph of eletriptan hydrobromide
Breadth	Broad chemical coverage	Narrow solid-form coverage
Main invalidity issues	Novelty, obviousness, enablement	Polymorph selection, characterization, obviousness
Generic design-around	Difficult while core patent was active	Possible through alternate polymorph or process
Product testing	Chemical identity	XRPD and infrared characterization
Expiration	Earlier	Later
Current status	Expired	Expired

What licensing and settlement issues affected the patent landscape?

The patent record does not establish a continuing license or settlement right that remains commercially operative after expiration. Any historical settlement could have governed an authorized generic launch date, supply arrangement or agreed entry date, but such arrangements do not restore exclusivity after patent expiration.

The main commercial issue was timing. A generic company could accept a later entry date in exchange for avoiding litigation costs or securing a license. Once the patent expired, a settlement could no longer prevent nonparty generic entry, FDA approval or ordinary competition unless supported by a separate enforceable commercial agreement.

What manufacturing and geographic barriers remain?

US 6,110,940 was a United States patent. Its expiration eliminates the US patent barrier, but equivalent foreign patents could have created different timing in Europe, Canada, Japan or other markets.

Solid-form patents are often jurisdiction-specific. The same alpha polymorph may be protected by separate national patents with different claim language, expiration dates and validity outcomes. A manufacturer therefore must distinguish:

US product claims.
Foreign polymorph claims.
Process patents covering the manufacturing site.
Regulatory data and market exclusivity.
Trade-secret crystallization parameters not disclosed in the patent.

For current US supply, the expired patent does not block manufacture or sale. Manufacturing know-how, impurity control, batch reproducibility and regulatory compliance remain operational barriers, but they are not continuing exclusivity rights under this patent.

Key Takeaways

US 6,110,940 is a polymorph patent for the alpha form of eletriptan hydrobromide, the active ingredient in Relpax.
Claim 1 is the central product claim; claims 2 and 3 define the alpha form through infrared and XRPD data.
Claims 8 through 10 protect selected hydrogen bromide treatment, crystallization and polymorph-conversion processes.
The patent lists migraine and other 5-HT1-related conditions, but the principal approved use was acute migraine treatment.
The patent was narrower than the core eletriptan compound patent but could extend practical protection for the commercial solid form.
The patent expired on or about December 19, 2017, removing its current US blocking effect.
Eletriptan is a small molecule; biosimilar analysis is not applicable.
Generic competition proceeds through the ANDA pathway, with Paragraph IV challenges relevant during the patent term.
The patent does not broadly claim tablet formulations, controlled release, excipient systems or every eletriptan manufacturing process.

FAQs

Is US 6,110,940 a patent on eletriptan itself?

No. It is principally a patent on the alpha-polymorphic form of eletriptan hydrobromide and selected processes for making that form.

Does the patent cover eletriptan tablets at every strength?

The composition claims are not limited to a particular strength. They cover compositions containing the claimed compound or alpha polymorph in an effective amount, subject to the legal requirements of the claims.

Can a generic company use a different eletriptan polymorph?

During the patent term, a different polymorph could reduce risk under the alpha-form claims, but the manufacturer would still need to assess the core compound patent, other listed patents and any process claims. After expiration of US 6,110,940, the patent itself does not prevent use of another polymorph.

Is an infrared spectrum alone sufficient to identify the patented form?

The patent uses infrared data in claims 2 and 8, but claim 3 and claim 10 also use powder X-ray diffraction. In practice, polymorph identification would normally evaluate multiple analytical characteristics rather than rely on a single spectrum.

Does expiration of US 6,110,940 permit immediate generic launch?

Expiration removes the patent barrier, but a generic manufacturer still needs FDA approval, an accepted ANDA, bioequivalence and compliant labeling. Other patents, regulatory exclusivity or litigation involving separate patents could affect the launch date.

References

U.S. Patent No. 6,110,940. (2000). Polymorphic forms of eletriptan hydrobromide. United States Patent and Trademark Office.
U.S. Patent No. 5,545,644. (1996). Indole derivatives. United States Patent and Trademark Office.
U.S. Food and Drug Administration. (n.d.). Relpax: Prescribing information. FDA.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations. FDA.
U.S. Patent and Trademark Office. (n.d.). Patent term calculator. USPTO.
Food and Drug Administration. (1984). Drug Price Competition and Patent Term Restoration Act of 1984. 21 U.S.C. § 355(j).

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
United Kingdom	9417310	Aug 27, 1994

PCT Information
PCT Filed	May 17, 1995	PCT Application Number:	PCT/EP95/01914
PCT Publication Date:	March 07, 1996	PCT Publication Number:	WO96/06842

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
African Regional IP Organization (ARIPO)	576	⤷ Start Trial
African Regional IP Organization (ARIPO)	9500754	⤷ Start Trial
Austria	163182	⤷ Start Trial
Australia	2735295	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 6,110,940

Summary for Patent: 6,110,940