Last Updated: September 24, 2026

Details for Patent: 7,064,148


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Summary for Patent: 7,064,148
Title:Chloride channel opener
Abstract:Disclosed is a novel use of a prostaglandin compound as a chloride channel opener. According to the instant invention, chloride channels in a mammalian subject can be opened by a prostaglandin compound to facilitate chloride ion transportation.
Inventor(s):Ryuji Ueno, John Cuppoletti
Assignee: Sucampo GmbH
Application Number:US10/231,341
Patent Litigation and PTAB cases: See patent lawsuits and PTAB cases for patent 7,064,148
Patent Claim Types:
see list of patent claims
Use;
Patent landscape, scope, and claims:

United States Patent 7,064,148: Claim Scope, Drug Coverage, Expiration, and Patent Landscape

U.S. Patent No. 7,064,148 covers methods of treating diseases associated with impaired chloride-channel activity by administering defined prostaglandin compounds. Its strongest commercial relevance is to lubiprostone, marketed as Amitiza, because lubiprostone is a prostaglandin-derived chloride-channel activator used for constipation and related gastrointestinal indications. The patent is no longer an enforceable barrier in the United States because its ordinary patent term expired in 2022. Its historical importance was greater than its current blocking value because it combined broad Markush compound language with method-of-treatment claims directed to chloride-channel activation, cystic fibrosis, constipation, and other diseases. [1, 2]

What does U.S. Patent 7,064,148 cover?

The patent covers administering a prostaglandin compound to open ClC chloride channels or treat conditions associated with reduced chloride-ion permeability.

The claims have three principal layers:

Claim group Claims Technical and therapeutic scope
ClC-channel opening 1-12 Treatment of listed diseases by opening ClC channels with a defined prostaglandin compound
Cystic fibrosis 13-24 Treatment of cystic fibrosis with a halogen-substituted prostaglandin compound
Reduced chloride permeability 25 Treatment of selected diseases associated with reduced chloride permeability

Claim 1 is the broadest independent claim in the first group. Claim 13 is an independent cystic-fibrosis method claim. Claim 25 is a separate independent method claim focused on reduced chloride permeability rather than expressly reciting opening ClC channels.

The patent is a use patent. It does not directly claim:

  • A pharmaceutical composition as such;
  • A tablet, capsule, softgel, or liquid dosage form;
  • A manufacturing process;
  • A specific dosing regimen;
  • A specific polymorph or crystal form;
  • A commercial product by brand name;
  • A broad genus of chloride-channel modulators outside the claimed prostaglandin structures.

Infringement historically would have required proof that a product was administered for a claimed indication and contained a compound within the structural scope of the relevant claim.

What compounds are covered by the patent?

The claims use a broad prostaglandin Markush structure. The covered compounds share a prostaglandin-like core with variable substituents and side chains.

The principal structural limitations are:

  • The ring substituents L, M, and N may be hydrogen, hydroxy, halogen, lower alkyl, hydroxyalkyl, or oxo.
  • At least one of L and M must be non-hydrogen.
  • The five-membered ring may contain one or more double bonds.
  • The A group may be hydroxymethyl, hydroxyacetyl, carboxylic acid, or a pharmaceutically acceptable salt, ether, ester, or amide.
  • The B group may be ethylene, ethenylene, or ethynylene.
  • The Z group contains substituted or unsubstituted hydrocarbon functionality defined through R4 and R5.
  • R1 may contain halogen, alkyl, hydroxy, oxo, aryl, oxygen, nitrogen, or sulfur substitution.
  • Ra may contain halogen, oxo, hydroxy, alkoxy, alkanoyloxy, cycloalkyl, aryl, or aryloxy substitution.

The dependent claims progressively narrow the genus to halogenated, fluorinated, keto, prostaglandin E, and amide compounds.

Which compounds are specifically named?

Claims 8, 9, 11, 12, 20, 21, 23, and 24 identify narrower chemical classes or individual compounds:

Claim Compound class or compound
8 13,14-dihydro-16,16-difluoro prostaglandin E1
9 13,14-dihydro-15-keto-16,16-difluoro-PGE1 or the 18-methyl analogue
11 13,14-dihydro-15-keto-16,16-difluoro-PGE1 N-ethyl amide
12 13,14-dihydro-15-keto-16,16-difluoro-PGF1α N-ethyl amide
20 13,14-dihydro-16,16-difluoro-PGE1
21 13,14-dihydro-15-keto-16,16-difluoro-PGE1 or 16,16-difluoro-18-methyl-PGE1
23 13,14-dihydro-15-keto-16,16-difluoro-PGE1 N-ethyl amide
24 13,14-dihydro-15-keto-16,16-difluoro-PGF1α N-ethyl amide

The 16,16-difluoro and 15-keto limitations are commercially important because they track the structural family associated with lubiprostone and related Sucampo prostaglandin compounds. A commercial product does not infringe merely because it is a prostaglandin or activates chloride transport. It must fall within the claimed structural limitations and be used in a claimed treatment context.

How does the patent relate to lubiprostone and Amitiza?

Lubiprostone is a locally acting prostaglandin derivative that activates intestinal chloride secretion through epithelial chloride channels, particularly ClC-2-related transport mechanisms. Amitiza was approved by the FDA for chronic idiopathic constipation and later for irritable bowel syndrome with constipation in women and opioid-induced constipation in adults with chronic noncancer pain. [3]

The patent’s commercial relevance arises from overlap between:

  1. The claimed 13,14-dihydro prostaglandin structures;
  2. The 16,16-difluoro substitution pattern;
  3. The 15-keto prostaglandin classes;
  4. The chloride-channel mechanism;
  5. The constipation treatment claims.

The patent is broader than the approved Amitiza label in disease coverage. Claim 1 includes constipation, asthma, bronchitis, anxiety, insomnia, epilepsy, neuropathy, anesthesia, myotonia atrophica, and calculus renum. Claim 13 covers cystic fibrosis. Claim 25 covers a narrower list of conditions associated with reduced chloride permeability.

This creates a distinction between patent scope and FDA-approved use. The patent claims certain unapproved or development-stage uses, but regulatory approval does not establish infringement of every patent claim. Conversely, an FDA-approved indication may fall within a patent claim even when the patent also covers non-approved indications.

What are the strongest claims in U.S. Patent 7,064,148?

Claims 1, 13, and 25 are the enforceable anchors because they are independent claims.

Claim 1: broad ClC-channel method claim

Claim 1 requires:

  • A mammalian subject;
  • A listed disease;
  • Administration of an effective amount;
  • A prostaglandin compound within the claimed formula;
  • Treatment by opening ClC channels.

The claim has broad disease coverage but carries a potentially significant mechanism-of-action limitation. The patentee would need to establish that the accused use opens ClC channels or that the claim’s functional language is satisfied under the applicable claim-construction standard.

The compound definition is broad, but the claim requires at least one of L and M to be other than hydrogen. That limitation excludes unsubstituted members of some prostaglandin families.

Claim 13: cystic-fibrosis claim

Claim 13 is structurally similar to claim 1 but is directed specifically to cystic fibrosis. It adds a requirement that Ra be substituted by halogen.

This halogen requirement materially narrows the claim. The claim is potentially relevant to halogenated prostaglandin compounds designed to increase epithelial chloride transport, but it does not cover every compound within the general formula.

Claim 25: reduced chloride-permeability claim

Claim 25 covers treatment of a condition associated with reduced chloride-ion permeability. It omits constipation, asthma, and bronchitis from the disease list and includes:

  • Myotonia atrophica;
  • Calculus renum;
  • Anxiety;
  • Insomnia;
  • Epilepsy;
  • Anesthesia;
  • Neuropathy.

The claim also contains what appears to be a transcription error in the A-group definition, stated as “—COGH” rather than the chemically expected “—COOH.” The issued patent, prosecution history, and official patent text control the interpretation of that language. [1]

What formulations are protected by U.S. Patent 7,064,148?

The patent does not claim a specific formulation architecture. Its claims cover administration of the active prostaglandin compound and therefore may reach products containing a covered compound when used for a covered indication.

The patent does not expressly require:

  • A particular excipient;
  • A particular dosage form;
  • A particular release profile;
  • A particular particle size;
  • A particular capsule shell;
  • A particular concentration;
  • A particular route of administration.

The formulation-related risk therefore depends on the active ingredient and the use, not on the dosage form alone.

For Amitiza, later patents and regulatory records are more important for formulation, dosing, and product-specific protection than U.S. Patent 7,064,148. A generic manufacturer could avoid a formulation patent while still facing a method claim, or avoid the method claim through labeling while still facing a composition or formulation patent.

When did U.S. Patent 7,064,148 expire?

The patent’s U.S. term expired in 2022. The patent is therefore not a current U.S. exclusionary right against generic manufacture, sale, or use. Historical Orange Book listing and litigation relevance should be separated from present enforceability. [1, 2]

Event Date or period
Earliest priority period 1999
U.S. patent issuance June 20, 2006
Patent number U.S. 7,064,148
U.S. term end 2022
Current status Expired; no current blocking term

Patent expiration does not erase past infringement claims that accrued before expiration. It also does not eliminate other patents covering the same product, formulation, dosing regimen, crystalline form, or method of use.

What was the Orange Book status of U.S. Patent 7,064,148?

U.S. Patent 7,064,148 was associated with the Amitiza patent estate and was relevant to FDA-listed patent protection for lubiprostone products. Orange Book status must be evaluated by product and listing code because a patent can be listed for one NDA and not another. [2]

The Orange Book does not establish that every claim in a patent covers the approved product. It records the sponsor’s patent submission under FDA listing rules. Patent scope remains a matter of claim construction, infringement analysis, validity, and the specific NDA labeling.

For Amitiza, the broader patent estate included patents directed to:

  • Lubiprostone or related prostaglandin compounds;
  • Therapeutic use;
  • Chloride-channel activation;
  • Pharmaceutical compositions;
  • Product-specific methods;
  • Potentially later formulation or dosing limitations.

The expiration of 7,064,148 did not necessarily mark the end of all Amitiza patent protection. Later-expiring patents were more relevant to generic entry after 2022.

Which companies challenged the Amitiza patent estate?

Amitiza was subject to the standard abbreviated new drug application and Paragraph IV framework. Generic applicants challenged listed patents through certifications that the patents were invalid, unenforceable, or would not be infringed. The litigation environment included major generic manufacturers such as Dr. Reddy’s Laboratories, Mylan, Teva, Par Pharmaceutical, Amneal, and Zydus-related entities, depending on the product, filing period, and asserted patent. [4, 5]

The commercial consequences of those challenges included:

  • ANDA litigation under 35 U.S.C. § 271(e)(2);
  • Settlement agreements;
  • Potential authorized-generic arrangements;
  • Staggered launch rights;
  • Entry dates linked to patent expiry or settlement terms.

The relevant question for a current entrant is no longer whether 7,064,148 can independently block entry. The relevant question is whether any later-expiring patent remains listed against the intended lubiprostone product and whether the proposed label, formulation, or manufacturing process falls within those claims.

What Paragraph IV risks existed for generic lubiprostone?

The principal Paragraph IV risks were:

  1. Invalidity challenges against the compound, use, and formulation patents;
  2. Non-infringement arguments based on a narrower generic label;
  3. Carve-outs for non-patented indications;
  4. Arguments that the generic product did not practice the claimed mechanism;
  5. Challenges to written description, enablement, obviousness, anticipation, and indefiniteness.

A generic applicant could attempt a section viii labeling carve-out for patented indications. That strategy would not necessarily avoid infringement if the remaining label still encouraged a patented use or if the active ingredient and instructions inherently practiced the claimed method.

The method claims in 7,064,148 were vulnerable to ordinary use-patent defenses because they combine broad chemical genus language with functional treatment language. The specific dependent claims were narrower and easier to map chemically, but narrower claims may face stronger prior-art or obviousness attacks if the cited fluorinated prostaglandin compounds were disclosed or predictable.

How strong was the patent estate for lubiprostone?

The patent estate was commercially meaningful before expiration but should be characterized as layered rather than uniformly strong.

Estate component Strategic value Principal vulnerability
Broad prostaglandin genus Potentially wide chemical coverage Written description, enablement, and construction disputes
16,16-difluoro species Stronger product mapping Prior art and obviousness
15-keto species Product-specific narrowing Limited coverage if product structure differs
ClC-channel use Mechanistic differentiation Proof of mechanism and induced infringement
Constipation method Direct commercial relevance Label carve-out and divided-use issues
Cystic-fibrosis method Broad therapeutic concept Limited relevance if not commercially pursued
Formulation patents Product-level protection Design-around opportunities
Later patents Extended exclusivity Claim-by-claim validity and infringement risk

The narrower compound claims generally provided better product mapping than the broad disease claims. The broad disease claims could cover more uses, but they also created greater validity and proof issues.

What patent litigation affected U.S. Patent 7,064,148?

The patent was part of the historical Amitiza generic-entry dispute rather than a standalone platform patent litigation program. Litigation typically focused on the listed Amitiza patent portfolio as a group, not on 7,064,148 in isolation.

The principal legal issues were:

  • Whether the ANDA filing constituted technical infringement;
  • Whether the proposed generic label induced infringement;
  • Whether the asserted claims were invalid;
  • Whether the generic could omit patented indications;
  • Whether settlements delayed or permitted entry;
  • Whether later patents remained enforceable after 7,064,148 expired.

Because the patent expired in 2022, no current U.S. litigation involving this patent can preserve an exclusionary term beyond its expiration date. Any present Amitiza litigation would more likely concern later patents, damages for pre-expiration activity, or unrelated regulatory and commercial issues.

Does the patent create biosimilar risk?

No conventional biosimilar risk exists for 7,064,148. Lubiprostone is a chemically synthesized small molecule, not a biologic. The relevant competitors are ANDA-based generic manufacturers, not biosimilar applicants under the Public Health Service Act.

The competitive risks are therefore:

  • Generic lubiprostone capsules;
  • Alternative lubiprostone dosage forms;
  • Other secretagogues;
  • Chloride-channel activators;
  • Guanylate cyclase-C agonists;
  • Osmotic and stimulant laxatives.

FDA approval of generic lubiprostone follows the Hatch-Waxman pathway. The Purple Book and biosimilar interchangeability rules do not govern this product. [2, 6]

How does lubiprostone compare with competing constipation drugs?

Product Active ingredient Main mechanism Regulatory pathway Patent risk profile
Amitiza Lubiprostone Chloride-channel activation and increased intestinal fluid secretion NDA Historical compound, use, and formulation patents
Linzess Linaclotide Guanylate cyclase-C agonist NDA Separate peptide and use patent estate
Trulance Plecanatide Guanylate cyclase-C agonist NDA Separate peptide and formulation estate
Motegrity Prucalopride 5-HT4 agonist NDA Small-molecule patent estate
Relistor Methylnaltrexone Peripheral μ-opioid receptor antagonism NDA Separate composition and use patents
Generic laxatives Various Osmotic, stimulant, or stool-softening effects OTC or ANDA Usually lower product-specific patent exposure

Expiration of 7,064,148 reduces the protection around the chloride-channel method concept, but it does not give lubiprostone a monopoly over the broader constipation market. The commercial differentiators are tolerability, indication, payer coverage, pricing, and generic substitution.

What geographic coverage does the patent have?

U.S. Patent 7,064,148 has territorial effect only in the United States. Corresponding foreign applications or national-phase patents may have existed in Europe, Japan, Canada, and other jurisdictions, but each required separate validity and expiration analysis.

A U.S. patent does not block:

  • Manufacture entirely outside the United States for non-U.S. sale;
  • Sale in jurisdictions where corresponding rights expired;
  • Use of a non-infringing compound;
  • Export activity unless U.S. statutory provisions apply;
  • Foreign regulatory approval.

For a global launch, the relevant analysis must separate U.S. patent term, European supplementary protection certificates, Japanese term extensions, and country-specific claim scope.

What manufacturing and IP barriers remain after expiration?

Expiration of 7,064,148 removes one historical barrier but does not eliminate technical or commercial barriers.

Potential remaining barriers include:

  • Later-expiring patents covering lubiprostone;
  • Patents on formulations or dosing;
  • Manufacturing-process patents;
  • Supplier exclusivity;
  • Drug-substance specifications;
  • Analytical methods;
  • Stability and impurity-control requirements;
  • FDA facility inspections;
  • ANDA bioequivalence requirements;
  • Controlled access to high-quality prostaglandin intermediates.

The patent itself does not claim a manufacturing process. A competitor that produces the same active ingredient through a different process would not infringe a process claim that is absent from this patent, although other patents could apply.

What generic launch scenarios existed and remain?

The principal launch scenarios were:

Launch after patent expiry

This is the lowest patent-risk path for claims that expired in 2022, subject to other listed patents.

Launch after settlement

A generic applicant could obtain a contractually defined entry date before the latest patent expiry. The settlement could include a licensed launch, an authorized generic arrangement, or restrictions tied to particular indications.

At-risk launch

A generic could launch before final resolution of listed patents. This would create exposure to damages, injunction requests, and substantial litigation costs.

Label carve-out

A generic could omit a patented indication if FDA rules permitted the carve-out and the resulting label did not encourage the patented use.

For current diligence, the most important scenario is a product-specific Orange Book review of all listed patents, followed by claim charts against the proposed active ingredient, dosage form, and label.

Key Takeaways

  • U.S. Patent 7,064,148 is a method-of-treatment patent centered on prostaglandin-mediated opening of ClC chloride channels.
  • Its claims cover broad prostaglandin Markush structures and narrower 16,16-difluoro, 15-keto, PGE1, PGF1α, and N-ethyl amide species.
  • Claims 1, 13, and 25 are the three independent claim groups.
  • The patent is historically relevant to lubiprostone and Amitiza.
  • It does not claim a specific tablet, capsule, formulation, manufacturing process, or polymorph.
  • The patent expired in 2022 and is not a current U.S. blocking right.
  • Generic competition is governed by the broader Amitiza patent estate, later-expiring patents, FDA listing status, and any settlement terms.
  • Biosimilar rules do not apply because lubiprostone is a chemically synthesized small molecule.
  • Current launch risk depends on later patents, label design, formulation, process rights, and ANDA requirements rather than on 7,064,148 alone.

FAQs

Does U.S. Patent 7,064,148 cover Amitiza directly?

It historically covered methods using prostaglandin compounds within the claimed structural genus, including compound classes associated with lubiprostone. The patent did not claim the Amitiza brand or every possible formulation of lubiprostone.

Can a generic company still be sued under Patent 7,064,148?

The patent’s ordinary U.S. term expired in 2022. New infringement occurring after expiration generally cannot be blocked through an injunction based on that patent, although pre-expiration conduct may raise historical damages issues.

Does the patent cover cystic-fibrosis treatment?

Yes. Claims 13 through 24 cover treatment of cystic fibrosis with qualifying halogen-substituted prostaglandin compounds.

Are the N-ethyl amide compounds commercially important?

They are important for claim analysis because claims 11, 12, 23, and 24 expressly identify them. Commercial relevance depends on whether the marketed product contains one of those amides rather than another member of the broader prostaglandin genus.

Does expiration of this patent eliminate all Amitiza exclusivity?

No. Other patents, regulatory exclusivities, settlement agreements, formulation rights, and later-expiring patents may have affected or continued to affect generic entry.

References

  1. United States Patent and Trademark Office. (2006). U.S. Patent No. 7,064,148: Treatment of disease by opening ClC channels. U.S. Department of Commerce. https://patents.google.com/patent/US7064148B2/en

  2. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book

  3. U.S. Food and Drug Administration. (2018). Amitiza (lubiprostone) prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/

  4. U.S. Food and Drug Administration. (2024). ANDA, patents, and exclusivity. https://www.fda.gov/drugs/abbreviated-new-drug-application-anda/anda-submissions-content-and-format

  5. U.S. Congress. (1984). Drug Price Competition and Patent Term Restoration Act of 1984, 21 U.S.C. § 355 and 35 U.S.C. § 271(e).

  6. U.S. Food and Drug Administration. (2024). Purple Book: Database of licensed biological products. https://purplebooksearch.fda.gov/

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Drugs Protected by US Patent 7,064,148

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

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