Details for Patent: 3,937,838
Summary for Patent: 3,937,838
| Title: | Orally active bronchospasmolytic compounds and their preparation | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Abstract: | Novel compounds are disclosed having useful activity as bronchodilators of improved longevity of action and reduced incidence of side effects. These compounds are described by the formula: ##EQU1## wherein R1 is a member of the class consisting of tertiary butyl and cyclobutyl, and R2 is a hydrogen or 2 to 5 carbon atom acyl radical, and pharmaceutically acceptable salts thereof. The activity of these compounds is compared to previously known bronchodilators such as 1-(3', 5'-dihydroxyphenyl)-2-(isopropylamino)-ethanol, having the common name orciprenaline, and 1-(3', 4'-dihydroxyphenyl-2-isoproplyamino-ethanol, having the common name isoprenaline. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inventor(s): | Kjell Ingvar Leopold Wetterlin, Leif Ake Svensson | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Assignee: | Draco AB | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Application Number: | US05/372,497 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Patent Claim Types: see list of patent claims | Use; Composition; | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Patent landscape, scope, and claims: | United States Patent 3,937,838: Terbutaline Scope, Expiration, Orange Book Status, and Patent LandscapeU.S. Patent No. 3,937,838 covers bronchodilator methods and pharmaceutical compositions containing terbutaline, selected terbutaline esters, and pharmaceutically acceptable salts. The patent is a historical composition-of-matter and therapeutic-use patent with no remaining exclusionary effect. Its pre-URAA patent term expired in the early 1990s, leaving generic terbutaline outside the patent's scope to the extent no later, unexpired patent applies. [1] What drug does U.S. Patent 3,937,838 protect?The central compound is terbutaline, chemically identified as 1-(3',5'-dihydroxyphenyl)-2-(tert-butylamino)ethanol. Terbutaline is a selective beta-2 adrenergic agonist used as a bronchodilator. The patent also identifies 1-(3',5'-diisobutyryloxyphenyl)-2-(tert-butylamino)ethanol, a diacylated terbutaline derivative. The claims extend to pharmaceutically acceptable salts of the claimed compounds.
The patent is directed to small-molecule pharmaceutical technology. It does not cover a biologic, biosimilar, inhaler device, nebulizer platform, or manufacturing process as an independent claim category. What are the claims of U.S. Patent 3,937,838?The claims divide into four groups: genus claims, compound-specific claims, composition claims, and dosage-unit claims. Claim 1: therapeutic-use Markush claimClaim 1 covers a method of producing bronchial dilation in animals, including humans, by administering a therapeutically effective amount of an ethanol amine selected from the claimed chemical formulas. The claim also covers pharmaceutically acceptable salts. Its key limitations are:
The claim is a method-of-use claim, not a claim to every possible use of terbutaline. A use outside bronchodilation would not necessarily meet the stated therapeutic-purpose limitation. Claims 2 and 3: species claimsClaim 2 narrows claim 1 to terbutaline or a pharmaceutically acceptable salt. Claim 3 narrows claim 1 to the diisobutyryl terbutaline derivative or a pharmaceutically acceptable salt. These claims are species claims because they identify specific compounds within the broader chemical genus of claim 1. Claim 4: composition claimClaim 4 covers a composition for producing bronchial dilation containing:
The carrier limitation distinguishes the composition claim from the method claim. The claim reaches pharmaceutical preparations containing the active compound, but it does not expressly require a particular tablet, aerosol, injectable, syrup, or inhalation device. Claim 5: terbutaline compositionClaim 5 narrows claim 4 to terbutaline or a pharmaceutically acceptable salt. This is the principal composition claim directed to terbutaline itself. Claim 6: concentration rangeClaim 6 requires the claimed compound to be present at 0.1% to 20% by weight. A composition outside that concentration range could avoid claim 6 while potentially remaining within claim 4, depending on whether all other claim limitations are satisfied. Claim 7: dosage-unit rangeClaim 7 covers a dosage-unit form containing 0.05 mg to 50 mg of the claimed compound. This limitation focuses on the amount of active ingredient per dosage unit. A product could fall within claim 7 even if its total formulation weight, delivery mechanism, or excipient system differs from the examples in the patent. How broad is the chemical scope of the patent?The chemical scope is broader than terbutaline alone but narrower than all beta-2 agonists. The genus uses substituted phenyl ethanolamines with a tert-butylamino side chain and acyl-substituted phenolic groups. The acyl radical limitation in the supplied claim language covers 2- to 5-carbon fatty-acid-derived groups. That wording potentially reaches multiple ester variants, subject to the exact structures shown in the patent drawings and the rules of claim construction. The practical scope can be divided as follows:
The exact scope of the Markush claims depends on the formula drawings, substituent definitions, specification, prosecution history, and any disclaimer or amendment made during examination. The textual claims supplied establish the principal commercial scope but do not reproduce the chemical structures labeled in the patent figures. When did U.S. Patent 3,937,838 expire?U.S. Patent 3,937,838 was issued under the pre-URAA patent-term regime. Patents issued before June 8, 1995 generally received a term of 17 years from issuance, subject to terminal disclaimers, disclaimers, or statutory adjustments. [1,2] The patent was issued in 1976 and therefore expired in the early 1990s, approximately 17 years after issuance. It is not an active patent that can block a current generic terbutaline product.
The patent's expiration eliminates infringement risk based solely on U.S. Patent 3,937,838. It does not eliminate the possibility that a later patent could cover a particular formulation, dosage form, device, polymorph, manufacturing process, or combination product. What is the Orange Book status of U.S. Patent 3,937,838?U.S. Patent 3,937,838 has no current Orange Book exclusivity effect. The patent is expired and cannot support a current listed-patent barrier to an abbreviated new drug application. The Orange Book records patents that sponsors identify for approved drug products under the Hatch-Waxman framework. Patent listing is product-specific and does not convert an expired patent into a continuing regulatory barrier. [2] For terbutaline products, the commercial review should distinguish among:
An applicant relying on an expired compound patent would not face a current Paragraph IV certification directed to that patent as an enforceable barrier. A Paragraph IV challenge is relevant only when an unexpired patent is listed in the Orange Book for the reference product. Are there current Paragraph IV challenges involving this patent?No current Paragraph IV risk arises from U.S. Patent 3,937,838 because the patent expired decades ago. Historically, an ANDA applicant seeking approval for a product corresponding to a listed terbutaline drug could have addressed the patent through a certification under 21 U.S.C. ยง 355(j)(2)(A)(vii). Today, the patent cannot support:
Any current Paragraph IV issue would have to arise from a different, later-expiring patent. What formulation patents are relevant to terbutaline?The supplied patent claims pharmaceutical carriers, concentration ranges, and dosage-unit amounts, but they do not claim a modern delivery platform in technical detail. The patent does not independently claim:
Claims 4, 6, and 7 could have covered conventional pharmaceutical formulations containing terbutaline during the patent term. They do not create continuing protection for every later product that uses a carrier or falls within a historical dosage range. For freedom-to-operate purposes, a modern terbutaline product should be screened against later patents directed to:
Does the patent cover terbutaline sulfate?Yes, the claims expressly include pharmaceutically acceptable salts. Terbutaline sulfate would ordinarily fall within that salt language, assuming it is used in a claimed bronchodilator method or composition and the other claim limitations are met. The salt language extends the claims beyond the free base. It does not, however, create a new patent term for terbutaline sulfate. Once the underlying patent expired, the salt coverage expired with it. Does the patent cover albuterol or other beta-2 agonists?No. The patent does not automatically cover all beta-2 agonists. Albuterol, also known as salbutamol, has a different chemical structure. Levalbuterol is the active enantiomer of albuterol and is also structurally distinct from terbutaline. Formoterol and salmeterol contain different structural features and are not captured merely because they produce bronchodilation. The patent's therapeutic-use language does not expand the claims to every compound that produces bronchial dilation. The compound must first satisfy the claimed chemical structure. How does the patent compare with competing beta-2 agonist patent estates?
Terbutaline's original patent estate is commercially weak today because the central compound claims are expired. Competitive differentiation now depends on regulatory approvals, route of administration, formulation performance, supply economics, and later product-specific intellectual property. Which companies are challenging the patent?No current company has a meaningful litigation position against U.S. Patent 3,937,838 because the patent is expired. The original patent was associated with the development and commercialization of terbutaline technology, including Astra-related pharmaceutical interests. Current generic competition is based on the expiration of the compound patent and any subsequent regulatory pathway, not on an active dispute over the original claims. A historical assignee, licensee, or commercial sponsor would not retain an enforceable patent monopoly after expiration. Licensing arrangements may have affected commercialization during the patent term, but they do not extend the statutory patent term. What is the biosimilar risk?There is no biosimilar issue. Terbutaline is a chemically synthesized small molecule, not a biologic subject to the biosimilar pathway under the Public Health Service Act. The relevant competitive pathway is the ANDA process for generic drugs, or, depending on the product and regulatory history, another small-molecule approval route. The principal legal issues are generic-drug equivalence, labeling, dosage form, bioequivalence, and any later-listed patents. What generic launch scenarios exist for terbutaline?Because the original patent has expired, the principal generic launch scenarios are: Conventional oral productA generic tablet or other oral dosage form can compete without waiting for U.S. Patent 3,937,838. The applicant must satisfy FDA requirements for the applicable reference product and demonstrate pharmaceutical equivalence and bioequivalence where required. [3] Injectable productAn injectable terbutaline product may face manufacturing, sterility, stability, and supply-chain barriers. Those are regulatory and technical barriers, not barriers created by the expired patent. Inhaled productAn inhaled product may encounter more complex device, formulation, and bioequivalence requirements. Any relevant patent risk would likely arise from later delivery-system or formulation patents rather than from U.S. Patent 3,937,838. Reformulated productA modified-release or novel-delivery product may obtain separate intellectual-property protection if it satisfies patentability requirements. Such protection would not revive the expired terbutaline compound claims. How strong is the patent estate?The estate was strong during its effective term for products containing terbutaline because claims 2 and 5 expressly identified the active ingredient and its salts. The composition claims also reached pharmaceutical preparations containing the compound. Its current strength is zero as an exclusionary right because the patent expired.
Key Takeaways
FAQs About U.S. Patent 3,937,838Does U.S. Patent 3,937,838 still block generic terbutaline?No. The patent expired in the early 1990s and no longer blocks generic terbutaline. Was terbutaline protected by a composition-of-matter patent?Yes. Claims 2 and 5 specifically identify terbutaline, while broader claims cover related ethanol amines and salts. Does the patent cover terbutaline inhalers?Only to the extent an inhaler formulation satisfied the composition limitations during the patent term. The patent does not independently claim a specific inhaler device or modern inhalation platform. Can a company obtain a new patent on a terbutaline formulation?Potentially. A later formulation patent would need to satisfy novelty, nonobviousness, written-description, enablement, and other statutory requirements. It would not extend the expired original compound patent. Is terbutaline subject to biosimilar competition?No. Terbutaline is a small-molecule drug. Competition proceeds through generic-drug regulatory pathways rather than biosimilar approval. References
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Drugs Protected by US Patent 3,937,838
| 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: 3,937,838
| Foriegn Application Priority Data | ||
| Foreign Country | Foreign Patent Number | Foreign Patent Date |
| 14182/66 | Oct 19, 1966 | |
International Family Members for US Patent 3,937,838
| Country | Patent Number | Estimated Expiration | Supplementary Protection Certificate | SPC Country | SPC Expiration |
|---|---|---|---|---|---|
| Austria | 286964 | ⤷ Start Trial | |||
| Austria | 287678 | ⤷ Start Trial | |||
| Austria | 287679 | ⤷ Start Trial | |||
| >Country | >Patent Number | >Estimated Expiration | >Supplementary Protection Certificate | >SPC Country | >SPC Expiration |
