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Details for Patent: 5,223,510
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Summary for Patent: 5,223,510
| Title: | Alkylaminoalkyl derivatives of benzofuran, benzothiophene, indole and indolizine, process for their preparation and compositions containing them | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Abstract: | The subject of the invention is benzofuran, benzothiophene, indole or indolizine compounds of general formula: | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inventor(s): | Jean Gubin, Pierre Chatelain, Jean Lucchetti, Gilbert Rosseels, Henri Inion | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Assignee: | SABIFU , Sanofi SA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Application Number: | US07/736,580 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Patent Claim Types: see list of patent claims | Use; Composition; | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Patent landscape, scope, and claims: | US Patent 5,223,510: Claim Scope, Dronedarone Coverage, Expiration and Patent LandscapeUS Patent 5,223,510 is the foundational U.S. composition-of-matter patent covering dronedarone and a broad family of benzofuran, benzothiophene, indole and indolizine cardiovascular compounds. Its strongest commercial claim is claim 10, which expressly recites dronedarone and related analogs. The patent issued on June 29, 1993, and, under the pre-Uruguay Round Agreements Act 17-year term applicable to the patent, expired on June 29, 2010.[1] The patent no longer blocks generic dronedarone entry. FDA approval of Multaq occurred in 2009, with subsequent regulatory exclusivity periods ending years after the composition patent expired. Because dronedarone is a small molecule, the relevant competitive pathway is an ANDA with Paragraph IV or Paragraph III certifications, not a biosimilar application.[2][3] What drug does US Patent 5,223,510 protect?The patent covers dronedarone and a large Markush genus of substituted heteroaromatic compounds. The commercially important compound is:
Claim 10 expressly lists:
That compound corresponds to dronedarone in its free-base form. The patent also covers pharmaceutically acceptable salts, including the hydrochloride salt used in Multaq. How does the claimed compound correspond to dronedarone?The dronedarone structure maps onto the claim as follows:
The patent specification and claim set therefore cover both the structural class and the specific active ingredient later developed as Multaq. How broad is claim 1 of US Patent 5,223,510?Claim 1 is a broad Markush composition-of-matter claim. It covers multiple heteroaromatic cores, multiple substituent families and multiple side-chain architectures. The principal scope has five layers. 1. Heteroaromatic coreThe claim reaches compounds based on:
This is materially broader than dronedarone, which uses only the benzofuran core. 2. Sulfonamide and amino substituent optionsThe claim permits numerous substituent combinations involving:
The definition of R and Ra allows sulfonamide-related and amino-substituted variants. Claim 2 narrows the combination to R as a sulfonyl group and Ra as hydrogen, which corresponds to the methylsulfonamido arrangement in dronedarone. 3. Aromatic acyl and ether linkageThe claim covers compounds containing an aromatic carbonyl substituent linked to an oxygen- or sulfur-containing chain. Claim 3 narrows Y to a defined arrangement, while claims 4 and 5 specify benzoyl and 4-benzoyloxy-related structures. Dronedarone falls within the benzoyl subclass and contains a para-substituted phenoxypropyl side chain. 4. Terminal amine side chainsThe claim permits:
Claim 6 narrows R1, R2 and R3 to n-butyl groups and sets n at 3. That limitation corresponds closely to the di-n-butylaminopropoxy side chain of dronedarone. 5. Heteroatom and ring-system alternativesThe claim permits X and A to be oxygen, sulfur or, in specified cases, nitrogen-containing linkages. W, W' and Z define alternative ring and unsaturation arrangements. These provisions expand the genus to several related heterocyclic and heteroatom-containing structures. The result is a structurally extensive genus that reaches well beyond the approved drug. Which claims directly cover dronedarone?Claims 2, 6, 7, 8, 9 and 10 are the most relevant claims for dronedarone.
Claim 10 is the most commercially significant because it names the specific dronedarone compound rather than relying solely on the broader structural formula. What formulations are protected by US Patent 5,223,510?The patent protects pharmaceutical compositions containing a claimed active compound with a pharmaceutical vehicle or excipient. Claims 11 and 12 cover:
The claims do not require a particular tablet composition, dissolution profile, coating, particle size, polymorph or manufacturing process. They are composition claims at a high level. The patent does not appear, from the supplied claims, to require:
A later formulation patent could therefore have provided narrower protection for a commercial tablet, even though the broad composition claim in US 5,223,510 has expired. What method-of-use patents and therapeutic claims are included?Claims 13-20 cover treatment and medical-use applications for:
The claimed dose range is 50 to 500 mg of active ingredient for the treatment claims in claims 13, 15, 16 and 17. Claims 14 and 18-20 are medical-use claims directed to combining the compound with a pharmaceutical vehicle or excipient to produce a medicine for the listed conditions. How strong are the method claims?The method claims were narrower and commercially less important than the composition claims because they require:
The arrhythmia claims were the closest to the eventual commercial use of dronedarone. The original patent claims, however, do not define the modern Multaq label indication, which is more specific than a general arrhythmia treatment claim.[2] Are the veterinary claims enforceable?Claims 21-26 address veterinary compositions and veterinary treatment methods. Claims 22-25 contain a dependency problem: they refer to a "veterinary composition according to claim 11," while claim 11 is directed to a pharmaceutical composition rather than the veterinary composition in claim 21. That drafting issue creates a potential clarity and claim-construction vulnerability. Claim 26 separately covers veterinary compositions containing a claim 10 compound and is less dependent on the defective wording in claims 22-25. The veterinary claims had no apparent relevance to the human Multaq product. When did US Patent 5,223,510 expire?
US Patent 5,223,510 was issued before the change to the 20-year-from-earliest-effective-filing-date regime. Its term was therefore governed by the former 17-year-from-issue rule.[1] No current patent-term extension can make the original patent an active patent today. Any regulatory exclusivity associated with Multaq was separate from the patent term and did not revive US 5,223,510. What is the Orange Book status of US Patent 5,223,510?US Patent 5,223,510 was historically associated with Multaq and dronedarone hydrochloride. Its Orange Book significance was as an expired composition-of-matter patent. The Orange Book distinguishes between:
An expired listed patent does not create a current patent barrier. An ANDA applicant would generally not need to make a Paragraph IV challenge to an expired patent. The relevant certification would ordinarily be Paragraph III if the patent remained listed but expired before approval, or the patent may no longer have practical blocking significance in the active listing analysis.[3] Which companies challenged the patent under Paragraph IV?The patent and claim text do not identify any ANDA challenger, settlement agreement or litigation defendant. The patent itself cannot establish the identity of later generic challengers. The key legal point is that any Paragraph IV dispute involving US 5,223,510 would have been time-limited by the June 29, 2010 expiration date. FDA approval of Multaq occurred close to the end of the patent term, and the five-year NCE exclusivity period extended beyond the patent expiration date. That timing reduced the commercial value of a Paragraph IV challenge to the original patent alone. A later generic applicant would have focused on:
Did the patent protect the Multaq formulation?US 5,223,510 protected compositions containing the claimed active compounds, including dronedarone. It did not, based on the supplied claims, claim a detailed commercial formulation. The patent’s formulation protection is therefore broad in subject matter but limited in technical specificity. It could cover a composition containing dronedarone and an excipient, but it does not establish protection for a particular:
Any such protection would have to arise from a separate patent or regulatory exclusivity provision. How does the patent estate compare with competing antiarrhythmic drugs?US 5,223,510 had a stronger historical position than a typical method-of-use patent because it covered the active molecule itself. Composition-of-matter protection generally blocks substitution with the same active ingredient until expiration, regardless of formulation differences.
Dronedarone has no biosimilar risk because it is a chemically synthesized small molecule. Competition is based on generic-drug approval, not the Public Health Service Act biosimilar pathway. How strong was the patent estate?The estate had high historical strength for the specific active ingredient and weaker relative strength for broad genus coverage. Strongest elements
Potential vulnerabilities
Those vulnerabilities were commercially secondary after expiration. They would have mattered most during pre-expiration validity litigation. What generic launch scenarios existed?Three launch scenarios were commercially relevant. Paragraph III launchA generic applicant could acknowledge the patent and wait until its expiration. For US 5,223,510, that date was June 29, 2010. Paragraph IV challengeAn applicant could allege that the patent was invalid, unenforceable or not infringed. A timely Paragraph IV notice could trigger Hatch-Waxman litigation and a 30-month stay, subject to the statutory requirements and Orange Book listing status.[4] Post-exclusivity launchAfter the NCE exclusivity period and expiration of any unexpired listed patents, an ANDA applicant could seek approval without challenging a live composition patent. This was the lowest litigation-risk scenario. The commercial launch analysis for dronedarone therefore depended more on later patents and FDA exclusivity than on US 5,223,510 after 2010. What licensing deals are associated with this patent?The patent is associated with the Sanofi dronedarone development program. The supplied claim text does not identify a license, assignment agreement, co-development agreement or royalty arrangement. Patent ownership and commercial sponsorship should be distinguished from licensing. The patent’s assignee history, any assignments recorded at the USPTO, and any Sanofi transaction documents would control ownership analysis. No licensing right can be inferred from the claim language itself. What manufacturing and IP barriers remain after expiration?Expiration of the composition patent removed the primary molecule-level barrier. Remaining barriers could include:
These barriers are narrower than composition-of-matter protection. A generic manufacturer can often design around them through an alternative process, formulation or solid form, but approval still requires pharmaceutical equivalence, bioequivalence and adequate chemistry, manufacturing and controls documentation. Key Takeaways
FAQsWhat is the chemical name of the drug covered by claim 10?Claim 10 covers dronedarone in free-base form, with the marketed product supplied as dronedarone hydrochloride. Does US Patent 5,223,510 cover amiodarone?No. The patent covers a genus of substituted heteroaromatic compounds that includes dronedarone and related compounds. It does not claim amiodarone as the active ingredient. Can a generic avoid claim 10 by using dronedarone hydrochloride instead of dronedarone free base?No practical distinction remains because claim 9 covers pharmaceutically acceptable salts, and the patent expired in 2010 in any event. Is a dronedarone extended-release tablet covered by this patent?The supplied claims do not require extended release or any specific release profile. A separate formulation patent would be needed for narrow extended-release protection. Does expiry of US Patent 5,223,510 eliminate all legal barriers to generic Multaq?No. It eliminates the original composition patent barrier. Later patents, FDA exclusivity, Orange Book listings, labeling provisions and formulation or process rights may still affect approval and launch timing. References
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Drugs Protected by US Patent 5,223,510
| 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 |
Foreign Priority and PCT Information for Patent: 5,223,510
| Foriegn Application Priority Data | ||
| Foreign Country | Foreign Patent Number | Foreign Patent Date |
| France | 90 10036 | Aug 06, 1990 |
International Family Members for US Patent 5,223,510
| Country | Patent Number | Estimated Expiration | Supplementary Protection Certificate | SPC Country | SPC Expiration |
|---|---|---|---|---|---|
| Austria | 145645 | ⤷ Start Trial | |||
| Australia | 648569 | ⤷ Start Trial | |||
| Australia | 8142891 | ⤷ Start Trial | |||
| Brazil | 9103354 | ⤷ Start Trial | |||
| Canada | 2047773 | ⤷ Start Trial | |||
| Czechoslovakia | 9102427 | ⤷ Start Trial | |||
| >Country | >Patent Number | >Estimated Expiration | >Supplementary Protection Certificate | >SPC Country | >SPC Expiration |
