Details for Patent: 5,153,222
Summary for Patent: 5,153,222
| Title: | Method of treating pulmonary hypertension with benzidine prostaglandins | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Abstract: | The present invention is concerned with methods for the prophylaxis, treatment and diagnosis of pulmonary hypertension which comprise the administrative of an effective amount of a compound of formula (I) ##STR1## wherein a is an integer of from 1 to 3; X and Y, which may be the same or different, are selected from --O-- and --CH2 --;R is --(CH2)5 R1 wherein R1 is hydrogen or methyl, or R is cyclohexyl, orR is --CH(CH3)CH2 C.tbd.CCH3 ; andthe dotted line represents an optional double bond;or of a physiologically acceptable salt or acid derivative thereof.Medicaments and diagnostic aids for use in the methods of the invention are also within the scope of the invention. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inventor(s): | Anjaneyulu S. Tadepalli, Walker A. Long, James W. Crow, Kenneth B. Klein | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Assignee: | LRX PHARMACEUTICALS Inc , United Therapeutics Corp | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Application Number: | US07/715,439 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Patent Claim Types: see list of patent claims | Use; | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Patent landscape, scope, and claims: | US Patent 5,153,222: Treprostinil Pulmonary Hypertension Claims, Scope, Expiration, and Patent LandscapeUS Patent 5,153,222 covers the use of treprostinil, including pharmaceutically acceptable salts, to treat pulmonary hypertension. Its two claims are method-of-treatment claims. They do not claim treprostinil as a chemical compound, a particular formulation, a delivery device, or a manufacturing process. The patent was historically important for Remodulin, United Therapeutics’ injectable treprostinil product. Its enforceable term has expired. The patent therefore does not currently block generic treprostinil development, although later formulation, route-of-administration, and product-specific patents may have created separate barriers for particular products. What compound does US Patent 5,153,222 cover?The compound identified in both claims is treprostinil, also known as UT-15. The chemical name in the patent is:
Treprostinil is a prostacyclin analog that produces pulmonary and systemic vasodilation and inhibits platelet aggregation. It is marketed in several dosage forms, including injectable, inhaled, and oral products.
The claims use a chemical definition rather than the later generic name “treprostinil.” That definition is sufficiently specific to identify the active prostacyclin analog covered by the patent. What do the claims of US 5,153,222 require?Claim 1: administration of treprostinilClaim 1 requires:
The claim does not specify:
The phrase “comprises administering” makes the claim open-ended as to the steps included in the treatment regimen. The core required act is administration of the identified compound to a patient with pulmonary hypertension in an effective amount. Claim 2: administration of a pharmaceutically acceptable saltClaim 2 is directed to a pharmaceutically acceptable salt of the same compound. The principal commercial relevance is treprostinil sodium. Claim 2 therefore captures administration of treprostinil in salt form, provided the salt qualifies as pharmaceutically acceptable and the other claim elements are met. Claim 2 does not claim every treprostinil formulation independently. It claims the therapeutic use of a pharmaceutically acceptable salt. A formulation patent would require additional limitations, such as excipients, concentration, pH, stability characteristics, release profile, or device configuration. What is the legal scope of the patent?US 5,153,222 is narrower than a composition-of-matter patent and broader than a formulation-specific patent. What the patent does coverThe claims cover the therapeutic use of the defined treprostinil compound or its pharmaceutically acceptable salt for pulmonary hypertension. The absence of a route limitation gives the claims potentially broad historical coverage across routes of administration, subject to ordinary claim-construction principles and proof of infringement. The claims also do not limit pulmonary hypertension to idiopathic pulmonary arterial hypertension. The literal disease term is “pulmonary hypertension.” Depending on the applicable claim construction and evidence, the scope could reach treatment of pulmonary hypertension subtypes if the administered product and treatment purpose satisfy the claim. What the patent does not coverThe patent does not independently claim:
A party could not establish infringement merely by showing that a company manufactures treprostinil. The asserted conduct would generally need to involve administering the compound for pulmonary hypertension, inducing that administration, or contributing to an infringing use under the applicable statutory theory. When did US Patent 5,153,222 expire?The patent was filed on December 20, 1990, and issued on October 6, 1992. The patent term was extended in connection with FDA regulatory review of Remodulin. The FDA Orange Book historically listed US 5,153,222 for Remodulin with an expiration date of May 21, 2014. That date reflected patent-term extension under 35 U.S.C. § 156 rather than the ordinary pre-1995 patent term alone.[1][2]
The patent is therefore no longer a live exclusionary right. A patent expiration does not erase the historical relevance of the patent, but it removes the patent as a current basis for blocking an otherwise lawful generic product. What was the FDA and Orange Book status?Remodulin, treprostinil injection, received FDA approval on May 21, 2002, for subcutaneous administration and later for intravenous administration in patients with pulmonary arterial hypertension.[3] US 5,153,222 was listed in the Orange Book for Remodulin. Its listing related to the approved pulmonary hypertension use rather than to a composition-of-matter claim. FDA regulatory milestones
The FDA approval of Remodulin also supported regulatory exclusivity separate from patent protection. Remodulin received orphan-drug designation and approval for a rare disease indication. Orphan exclusivity is distinct from patent term and expired before the patent’s May 2014 expiration date.[3][4] Did US 5,153,222 protect Remodulin’s formulation?No. The patent’s claims do not require a specific formulation. A formulation infringement case would require a different patent or a different legal theory. The patent text supplied contains no limitation directed to:
This distinction matters because Remodulin, Tyvaso, and Orenitram use materially different product architectures. A patent covering injectable treprostinil use would not automatically cover an oral extended-release tablet or an inhaled solution as a formulation. What patent landscape surrounds treprostinil?The treprostinil patent estate developed in several layers. Foundational compound and therapeutic-use patentsEarly patents established the prostacyclin analog and its therapeutic use. US 5,153,222 belongs to the therapeutic-use layer. Because it does not claim the molecule as such, later applicants could pursue separate claims directed to salts, formulations, delivery systems, and specific routes. Injectable formulation patentsThe injectable product category has historically involved patent issues concerning:
These patents may be relevant to a generic injectable product even after expiration of US 5,153,222. Their applicability depends on the exact formulation, labeling, concentration, and device used by the proposed generic. Inhaled treprostinil patentsTyvaso introduced a separate patent category involving inhalation delivery. Relevant claim themes can include:
Those rights are analytically distinct from US 5,153,222. The older patent’s broad treatment language may have overlapped historically with inhaled administration, but later inhalation patents could have created additional, narrower protection. Oral extended-release patentsOrenitram created another patent layer involving:
A generic oral product would need to evaluate those patents separately from the expired 5,153,222 patent. Manufacturing and process patentsProcess patents may cover:
Process patents generally create a manufacturing risk rather than a direct risk from the clinical use claim in US 5,153,222. They are especially relevant when a generic sponsor uses a proprietary synthetic route or purchases an intermediate from a third party. How strong were the original claims?Scope strengthThe claims were commercially significant because they combined a defined treprostinil compound with the broad therapeutic indication of pulmonary hypertension. The absence of route and dose limitations increased their historical breadth. Validity strengthThe claims were vulnerable in ways typical of early method-of-use patents:
The patent’s issuance and FDA listing do not establish that every possible use of treprostinil would have been valid or enforceable. They establish that the patent was granted and used as a listed right for the approved product. Current strengthCurrent enforceability is zero because the patent term has expired. Its historical claim breadth does not revive the patent or extend later patents covering treprostinil products. Were there Paragraph IV challenges to US 5,153,222?A Paragraph IV certification would have been relevant while the patent remained listed and unexpired. A generic applicant could have asserted that the patent was invalid, unenforceable, or not infringed. Because the patent expired in 2014, a later ANDA applicant would generally not need to litigate US 5,153,222 as a live patent barrier. Generic litigation would instead focus on unexpired Orange Book patents associated with the specific treprostinil product and dosage form. The practical distinction is:
Which companies face competitive pressure from generic treprostinil?The principal originator is United Therapeutics, which commercializes Remodulin, Tyvaso, and Orenitram. Generic competition is most direct for injectable treprostinil because injectable products are more readily evaluated through an ANDA pathway than complex inhaled or extended-release products. Competition differs by product:
The expiration of US 5,153,222 removes a foundational use patent, but it does not guarantee immediate substitution across all dosage forms. What generic launch scenarios follow from expiration?Injectable treprostinilThe most favorable generic scenario is an injectable product with a formulation and label that avoid all unexpired product-specific patents. The sponsor could pursue an ANDA with a Paragraph III certification for expired patents and address remaining listed patents through certification or litigation. Inhaled treprostinilAn inhaled product may face more complex regulatory and patent issues. Even if it contains the same active ingredient, the nebulizer, device, route, dosage regimen, and approved labeling can create separate patent and regulatory questions. Oral extended-release treprostinilAn oral generic faces the highest formulation-specific risk because bioequivalence, release characteristics, tablet architecture, and food effects are central to approval. Expiration of the 5,153,222 use patent is not sufficient to establish freedom to launch an Orenitram-equivalent product. What is the geographic coverage of US 5,153,222?The patent has territorial effect only in the United States. It does not create rights in Canada, Europe, Japan, China, or other jurisdictions. International risk depends on the corresponding patent family members, national prosecution outcomes, local term rules, supplementary protection certificates, and local regulatory exclusivity. A US expiration analysis cannot be used as a global launch clearance. Does US 5,153,222 create biosimilar risk?No. Treprostinil is a chemically synthesized small molecule, not a biologic. The relevant FDA pathway is generally an ANDA under section 505(j), or in some cases a 505(b)(2) application, not a biosimilar application under the Public Health Service Act. The relevant competitive risks are:
Key Takeaways
FAQsDoes US 5,153,222 claim treprostinil sodium?Yes. Claim 2 covers a pharmaceutically acceptable salt of the named treprostinil compound. Treprostinil sodium is the principal commercial example. Does the patent cover oral treprostinil?Historically, the broad treatment language could reach administration of treprostinil by different routes if the claim elements were satisfied. The patent is expired, and current oral-product risk depends on later extended-release and formulation patents. Can a company sell generic treprostinil after the patent expired?Expiration of US 5,153,222 removes that patent as a barrier. The company must still satisfy FDA requirements and clear any unexpired patents covering the selected formulation, route, device, manufacturing process, or labeling. Is treprostinil protected by a composition-of-matter patent?US 5,153,222 is not a composition-of-matter claim. Treprostinil protection has historically involved multiple patent categories, including therapeutic use, formulations, delivery systems, and manufacturing processes. Does an expired method patent affect current treprostinil pricing?It can remain commercially relevant through historical market structure and the timing of generic entry, but it cannot independently support a current injunction or prevent lawful generic competition after expiration. References
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Drugs Protected by US Patent 5,153,222
| 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: 5,153,222
| Foriegn Application Priority Data | ||
| Foreign Country | Foreign Patent Number | Foreign Patent Date |
| United Kingdom | 8814438 | Jun 17, 1988 |
International Family Members for US Patent 5,153,222
| Country | Patent Number | Estimated Expiration | Supplementary Protection Certificate | SPC Country | SPC Expiration |
|---|---|---|---|---|---|
| Austria | 84417 | ⤷ Start Trial | |||
| Australia | 3652889 | ⤷ Start Trial | |||
| Australia | 623147 | ⤷ Start Trial | |||
| Canada | 1327524 | ⤷ Start Trial | |||
| Germany | 68904358 | ⤷ Start Trial | |||
| >Country | >Patent Number | >Estimated Expiration | >Supplementary Protection Certificate | >SPC Country | >SPC Expiration |
