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Details for Patent: 5,202,128
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Summary for Patent: 5,202,128
| Title: | Sustained release pharmaceutical composition | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Abstract: | The present invention relates to a pharmaceutical pellet composition having a core element including at least one highly soluble active ingredient and a core coating which is partially soluble at a highly acidic pH. The pharmaceutical composition provides a slow release of active ingredient at a highly acidic pH and provides a constant, relatively faster rate of release at a more alkaline pH such as that of the intestine. Oral administration of the pharmaceutical pellet composition of the present invention to a patient is effective to deliver to the blood levels of active ingredient within the therapeutic range and to maintain such levels over an extended period of time. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inventor(s): | Angelo M. Morella, Mark C. Fisher | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Assignee: | Alpharma Pharmaceuticals LLC | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Application Number: | US07/574,551 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Patent Claim Types: see list of patent claims | Use; Composition; Formulation; Dosage form; | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Patent landscape, scope, and claims: | US Patent 5,202,128: Scope, Claim Construction, Expiration, and Pharmaceutical Patent LandscapeUS Patent 5,202,128 covers multiparticulate, pH-dependent sustained-release pellets. Its central technical concept is a coating that combines an insoluble rate-controlling polymer, an enteric polymer, and an acid-soluble material. The coating is designed to begin releasing drug slowly in the stomach and release it faster after exposure to the higher pH of the intestine. The patent was directed particularly to highly water-soluble active ingredients, including morphine salts, and to 8-to-24-hour pain-treatment regimens. The patent issued on April 13, 1993, and its 17-year patent term expired in April 2010, subject to any applicable patent-term adjustment or terminal disclaimer. It therefore does not presently provide enforceable US exclusionary rights. [1][2] What does US Patent 5,202,128 protect?The patent protects a formulation architecture rather than a single drug molecule. The independent claims require a core pellet containing an active ingredient and a multipart coating with three functional components:
The percentages for claims 1, 10, 18, 24, 25 and 26 are calculated against the combined weight of the three coating components. The claims also require a functional release result: release must begin slowly in the stomach and proceed at a faster rate in the intestine. The broadest formulation claims are claims 1 and 10. Claim 1 covers a composition with a highly water-soluble active ingredient. Claim 10 narrows the active ingredient to an acid-addition salt of morphine. Claim 11 further limits the morphine salt to morphine sulfate. The patent’s scope is therefore defined by four linked requirements:
A formulation that merely contains ethyl cellulose and an enteric polymer would not necessarily fall within the claims. The acid-soluble component and the claimed functional release behavior are central limitations. How do the independent claims differ?The independent claims fall into three principal groups. Composition claims for soluble drugsClaim 1 covers a pH-dependent sustained-release pellet containing an active ingredient with aqueous solubility of at least 1 part drug in 30 parts water. This is a relatively broad drug-class limitation. It reaches numerous pharmaceutical categories, including antihistamines, antibiotics, cardiovascular agents, analgesics and opiate agonists. Claim 24 adds a narrower requirement that the matrix polymer be composed of specified polymers, including:
Claim 24 is narrower than claim 1 because it expressly limits the matrix polymer to the listed polymer classes. Morphine composition claimsClaim 10 covers the same three-component release system when the active ingredient is an acid-addition salt of morphine. Claim 11 specifies morphine sulfate. Claims 25 and 17 narrow the polymer and coating composition further. Claim 17, as supplied, contains a dependent-claim reference error to claim 49. The issued patent text should control over the provided transcription when evaluating enforceability or prosecution history. The substantive limitation recites a coating containing:
This narrow combination is more relevant to product-specific comparison than the broad genus in claim 10. Method-of-treatment claimsClaim 18 covers treatment of pain using the claimed pH-dependent pellet composition. Claims 19 through 23 narrow the method to acute or chronic pain and morphine acid-addition salts. Claim 20 specifies a unit dosage form administered over an interval of approximately 8 to 24 hours. Claims 21 through 23 identify morphine salts, including morphine sulfate and morphine hydrochloride. The method claims require both administration and use of a composition meeting the formulation limitations. They do not claim treatment with extended-release morphine generally. What formulations are protected by the patent?The patent identifies three coating technologies by function. Matrix polymerThe matrix polymer remains substantially insoluble throughout the stomach and intestinal pH range. Its role is to maintain a diffusion barrier and regulate drug release. The disclosed candidates include ethyl cellulose and acrylic or methacrylic polymers. Ethyl cellulose is particularly important because it creates a water-permeable but insoluble film. Quaternary ammonium methacrylate polymers, such as commercially available Eudragit-type materials, can alter permeability and release rate. Enteric polymerThe enteric polymer is intended to remain substantially insoluble in the stomach and dissolve or become substantially more permeable in the intestine. The claims list:
The enteric polymer does not perform the conventional function of completely preventing gastric release. The claims require sufficient gastric delay, but also require initiation of release in the stomach through the acid-soluble component. Acid-soluble compoundThe acid-soluble compound creates pores or channels as it dissolves in the stomach. The claim examples include:
This component distinguishes the invention from a conventional enteric-coated dosage form. The intended profile is not "no release in the stomach, followed by release in the intestine." It is slow initial gastric release followed by faster intestinal release. What are the key dependent-claim limitations?Claims 5 through 9 and 12 through 17 add technical limitations that narrow infringement exposure.
The functional limitations in claims 1, 10, 18, 24, 25 and 26 create potential claim-construction disputes. Terms such as "effective to allow," "slow rate," "faster rate," "therapeutically effective amount," and "predetermined interval" are dependent on formulation testing and the specification’s examples. How strong was the patent estate?The patent had meaningful historical breadth but limited present-day commercial strength because the patent expired in 2010. Historical strengthsThe patent’s strongest features were:
The combination of composition and method claims would have increased litigation leverage during the patent term, particularly where a branded product used morphine pellets with ethyl cellulose, a methacrylic acid copolymer and polyethylene glycol. Weaknesses and design-around opportunitiesThe estate also had technical vulnerabilities:
The patent does not broadly claim all extended-release morphine products. It claims a particular multiparticulate coating system and, in the method claims, administration of that system. When did US Patent 5,202,128 lose exclusivity?The patent issued on April 13, 1993. For a US utility patent filed before June 8, 1995, the ordinary term was 17 years from grant, not 20 years from the earliest effective filing date. On that basis, the ordinary expiration date was April 13, 2010. [1][2]
The expiration date should be confirmed against the USPTO patent record, including any patent-term adjustment, terminal disclaimer or reexamination certificate. The supplied claim set does not identify a later enforceable continuation or reissue. What was the Orange Book status of US Patent 5,202,128?US Patent 5,202,128 should not be treated as a currently operative Orange Book patent. The Orange Book lists patents submitted by new drug application sponsors for approved products, and listing status is product-specific. A patent may cover a formulation concept without being listed for every product that uses the active ingredient. [3] The patent is not a current barrier to an abbreviated new drug application based on its expired claims. It also does not create an active 30-month stay under Hatch-Waxman. A Paragraph IV certification against an expired patent would not produce the same litigation consequences as a challenge to an unexpired Orange Book patent. For morphine sulfate extended-release products, the operative patent landscape has historically included product-specific formulation patents, manufacturing patents and later-generation controlled-release technologies. Those patents must be reviewed separately from US 5,202,128. Which companies or products were most relevant to the patent?The patent is technically aligned with sustained-release morphine products using coated pellets, including technologies historically associated with Napp Pharmaceutical Group and its affiliates. The morphine pellet concept is also relevant to products such as Zomorph outside the United States and to broader controlled-release morphine development. The connection should not be overstated. A product containing extended-release morphine is not automatically covered. Product-specific analysis requires comparison of:
MS Contin, Kadian and other extended-release morphine products have used distinct formulation technologies and patent portfolios. Kadian, for example, is associated with extended-release morphine sulfate multiparticulate technology, but the relevant patent estate cannot be assumed to be identical to US 5,202,128. FDA product records and Orange Book listings must be reviewed by NDA and product presentation. [3][4] What patent litigation and Paragraph IV challenges affected this patent?The patent’s expiration eliminates current infringement litigation risk based solely on US 5,202,128. During its term, a generic applicant could have filed a Paragraph IV certification if the patent was listed against the relevant reference-listed drug. A Paragraph IV certification would have required a patent-specific analysis of validity, enforceability and infringement. The principal attack vectors would have included:
No current Paragraph IV exposure remains from this patent because the claims are expired. The existence of historical litigation or settlement activity cannot be inferred from the claim text alone. The USPTO and PACER records would control for a complete docket history. [1][5] How does the patent compare with later extended-release morphine patents?US 5,202,128 is a platform patent. Later morphine patents generally became more product-specific.
The patent’s broad platform claims would have been most valuable before later products developed independent formulation barriers. Its present value is primarily freedom-to-operate history, prior-art relevance and technology provenance. What manufacturing and intellectual-property barriers remain?Although US 5,202,128 is expired, manufacturing barriers can remain under other rights and under regulatory requirements. Relevant manufacturing variables include:
A generic or follow-on manufacturer may avoid the expired patent but still face:
For an ANDA, the central regulatory question is whether the proposed product is bioequivalent to the reference listed drug and whether all listed unexpired patents have been addressed. The expired status of US 5,202,128 removes one patent obstacle but does not resolve the complete regulatory or patent analysis. [3][4] What generic launch risks exist today?US 5,202,128 presents no current generic launch risk because it is expired. A launch assessment should instead focus on:
The patent may still be cited as prior art against later patents. Its disclosure of the three-component coating architecture could limit the ability of a later applicant to obtain broad claims covering the same combination. What is the commercial significance of the patent?The patent’s commercial significance was highest for sustained-release oral products containing highly soluble drugs, where a conventional insoluble matrix could release drug too quickly in the stomach or too slowly in the intestine. For morphine, the claimed objective was to reduce plasma-concentration fluctuation while maintaining an extended dosing interval. Claims 12 and 14 quantify that objective by requiring a faster intestinal release rate and sustained plasma concentrations. The patent no longer supports royalty collection or exclusion of competitors in the United States. Its continuing commercial relevance lies in:
Key Takeaways
FAQsIs US Patent 5,202,128 still enforceable?No. Its ordinary US patent term expired in April 2010, subject to confirmation of the official USPTO term record. Does the patent cover all extended-release morphine sulfate products?No. It covers morphine-containing pellet compositions that meet the specified three-component coating, polymer, percentage and release limitations. Does morphine sulfate in a capsule infringe the patent?Not necessarily. Capsule presentation alone does not determine infringement. The underlying pellets must satisfy the patent’s structural and functional limitations. Can a generic rely on the patent’s expiration?Yes. An expired patent cannot support a current infringement claim or a Hatch-Waxman 30-month stay. The generic must still address any other unexpired patents and FDA requirements. Are the polymer percentages measured against the entire dosage form?For the principal claims, the percentages are measured against the combined weight of components (a), (b) and (c), unless a claim separately specifies coating-based percentages for plasticizers or fillers. References
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Drugs Protected by US Patent 5,202,128
| 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: 5,202,128
| Foriegn Application Priority Data | ||
| Foreign Country | Foreign Patent Number | Foreign Patent Date |
| Australia | PJ2192 | Jan 06, 1989 |
International Family Members for US Patent 5,202,128
| Country | Patent Number | Estimated Expiration | Supplementary Protection Certificate | SPC Country | SPC Expiration |
|---|---|---|---|---|---|
| Austria | 133862 | ⤷ Start Trial | |||
| Austria | 167629 | ⤷ Start Trial | |||
| Australia | 4773290 | ⤷ Start Trial | |||
| Australia | 617573 | ⤷ Start Trial | |||
| Canada | 2007181 | ⤷ Start Trial | |||
| Germany | 69025208 | ⤷ Start Trial | |||
| >Country | >Patent Number | >Estimated Expiration | >Supplementary Protection Certificate | >SPC Country | >SPC Expiration |
