Details for Patent: 5,837,284
Summary for Patent: 5,837,284
| Title: | Delivery of multiple doses of medications | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Abstract: | Dosage forms for oral administration of a methylphenidate drug are provided. The dosage forms provide a substantially immediate dose of methylphenidate upon ingestion, followed by one or more additional doses at predetermined times. By providing such a drug release profile, the dosage forms eliminate the need for a patient to carry an additional dose for ingestion during the day. The dosage forms and methods provided are useful in administering methylphenidate and pharmaceutically acceptable salts thereof, which generally require one or more doses throughout the day. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inventor(s): | Atul M. Mehta, Andrew L. Zeitlin, Maghsoud M. Dariani | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Assignee: | Celgene Corp | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Application Number: | US08/892,190 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Patent Claim Types: see list of patent claims | Composition; Compound; Dosage form; | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Patent landscape, scope, and claims: | US Patent 5,837,284: Methylphenidate Dosage-Form Claims, Expiration, and Patent LandscapeUS Patent 5,837,284 protects multiparticulate, bimodal-release methylphenidate dosage forms. Its core concept is a single oral dosage form that delivers an immediate dose and a second methylphenidate dose after an approximately two-to-seven-hour delay. The claims cover coated particles, ammonio methacrylate polymers, talc-containing coatings, d-threo-methylphenidate hydrochloride, two-pulse release profiles, and once-daily formulations. The patent issued on November 17, 1998, and its recorded patent term expired in 2016. It therefore does not create a current US patent barrier to generic or follow-on methylphenidate products. Its historical importance is tied to Ritalin LA-type bimodal-release technology and related multiparticulate delivery systems. (USPTO, 1998; FDA, 2024) What technology does US Patent 5,837,284 protect?The patent protects oral methylphenidate products containing two pharmacokinetic release phases:
The delayed fraction is contained in drug-loaded particles coated with a pharmaceutically acceptable ammonio methacrylate copolymer. The coating controls drug release by limiting penetration of gastrointestinal fluid into the particle and delaying dissolution or diffusion of methylphenidate. The claims are directed to dosage forms rather than to methylphenidate as a chemical compound. They do not broadly claim all extended-release methylphenidate products. The protected subject matter is limited by the combination of:
The technology corresponds to a pulsatile or bimodal oral delivery profile rather than a conventional continuous-release matrix tablet. What are the independent claims in US Patent 5,837,284?The patent has five principal independent claim groups: claims 1, 23, 27, 28, and 29.
Claims 1 and 27 are particle-population claims. They require two groups of particles, with one group providing an immediate dose and the other group providing a delayed dose. Claim 23 is structurally different. It describes a particle with a drug-containing core, an ammonio methacrylate coating, and an exterior layer containing methylphenidate. That architecture can produce an immediate-release dose from the exterior layer and a delayed dose from the coated core. Claims 28 and 29 are performance claims. Claim 28 focuses on an in vitro two-pulse dissolution profile. Claim 29 focuses on an in vivo plasma concentration profile having two maxima with a limited difference in magnitude. How broad is claim 1 of US Patent 5,837,284?Claim 1 is broad relative to the dependent claims, but it still requires a specific combination of structural and functional limitations. A product would generally need to include:
Claim 1 does not require:
The claim therefore reaches a range of multiparticulate dosage forms, including products using different methylphenidate salts and different binders, provided that the delayed particles satisfy the specified composition and release function. The two-to-seven-hour delay is a material limitation. A product designed for continuous release without a distinct delayed pulse would have a weaker infringement case under claim 1. A product with a second pulse outside the claimed timing range would also present a noninfringement position, subject to claim construction and equivalents analysis. What formulations are protected by claims 2 through 22?Claims 2 through 22 narrow claim 1 by specifying the drug salt, polymer, filler, polymer ratio, and delay period. Methylphenidate salt limitationsClaims 2 through 6 specify pharmaceutically acceptable methylphenidate salts. Claims 5 and 6 narrow the formulation to dl-threo-methylphenidate hydrochloride. Claim 4 requires the immediate-release particle group to contain approximately 2% to 99% by weight methylphenidate salt. Claims 5 and 6 then identify dl-threo-methylphenidate hydrochloride as the salt. Filler limitationsClaims 7 through 12 address filler in the coating composition. The permitted filler group includes:
Claim 7 requires approximately 20% to 50% filler by weight based on the total weight of the copolymer. Claims 9 through 12 progressively narrow the limitation to talc and then to approximately 35% to 45%, 38% to 42%, and about 40% talc. These claims are narrower formulation claims. They are more vulnerable to design-around than claim 1 because a competing product could use a different filler or a different filler concentration while retaining the broader bimodal-release concept. Ammonio methacrylate polymer ratiosClaims 13 through 16 specify the ratio of acrylic groups to quaternary ammonium groups in the ammonio methacrylate copolymer:
Claim 17 requires two different ammonio methacrylate copolymers:
Claims 18 through 20 narrow the ratio of the first copolymer to the second copolymer to approximately 90:10 to 99:1, then 93:7 to 97:3, and finally about 95:5. These limitations define a mixed-polymer coating system. A formulation using only one polymer, a different polymer ratio, or a different ammonium-containing acrylic polymer could avoid the narrower claims while potentially remaining relevant to claim 1 or claim 23. Delay-period limitationsClaims 21 and 22 narrow the delayed dose to:
These claims align closely with a second methylphenidate pulse several hours after the immediate dose. What does claim 23 protect?Claim 23 covers a once-daily dosage form with a layered particle structure. It requires:
This claim differs from claim 1 because the immediate-release drug is expressly located on the exterior surface of the delayed-release coating. Claim 23 can therefore read on a single population of coated particles carrying an outer immediate-release drug layer, rather than requiring two physically separate particle groups. Claims 24 and 25 narrow claim 23 to:
Claim 26 adds the two-polymer coating system. Claim 30 specifies the polymer compositions more precisely as copolymers containing methyl methacrylate, ethyl acrylate, and trimethylammonium chloride, commonly abbreviated TAMCl, in ratios of 2:1:0.1 and 2:1:0.2. What protection do claims 27 through 29 provide for d-threo-methylphenidate?Claims 27 through 29 are directed specifically to d-threo-methylphenidate hydrochloride or a pharmaceutically acceptable d-threo-methylphenidate salt. Claim 27 requires:
Claim 28 protects an in vitro release profile with two temporally separated pulses. Claim 29 protects an in vivo plasma profile with two maxima separated by approximately two to seven hours, with the maxima differing by no more than approximately 30%. Claims 28 and 29 are commercially important because they are not limited solely to a named coating composition. They reach the specified performance profile. Enforcement would depend heavily on the test method, sampling protocol, interpretation of "pulse" and "maximum," and whether the accused product produces the claimed profile under the relevant conditions. When did US Patent 5,837,284 expire?US Patent 5,837,284 issued on November 17, 1998. Its recorded term expired in 2016, based on the patent’s effective filing and priority history. The patent is therefore expired and cannot support a new US infringement action for conduct occurring after expiration. (USPTO, 1998; Google Patents, 2024)
The patent’s expiration removes the patent-based exclusivity barrier. It does not eliminate the possibility that later patents could cover a particular product, manufacturing process, formulation improvement, salt, dosage strength, labeling method, or delivery device. What is the Orange Book status of US Patent 5,837,284?The patent was associated historically with the Ritalin LA product and the bimodal-release methylphenidate formulation technology. The current Orange Book status is legally different from the historical listing status because an expired patent no longer provides enforceable patent protection. The Orange Book distinguishes among:
A patent’s presence in the Orange Book does not extend its term. Once the listed patent expires, an ANDA applicant no longer needs to use a Paragraph IV certification against that expired patent as a basis for entry. The relevant regulatory issue becomes whether other unexpired patents remain listed for the reference product. (FDA, 2024a) Were Paragraph IV challenges or generic litigation associated with this patent?A Paragraph IV certification is used when an ANDA applicant asserts that a listed patent is invalid, unenforceable, or will not be infringed. The historical Ritalin LA generic landscape included patent certifications and litigation risk around extended-release methylphenidate capsules. The principal legal significance of US 5,837,284 is now historical because the patent expired in 2016. Any Paragraph IV challenge directed solely to this patent no longer creates a current patent stay or patent-based launch barrier. A current generic applicant would need to assess:
The expired status of 5,837,284 does not establish freedom to operate for every methylphenidate product. It removes only this patent from the active patent-risk analysis. Which companies and products are relevant to this patent landscape?The patent is most closely associated with bimodal-release methylphenidate products modeled on Ritalin LA. The commercial landscape includes:
The existence of a bimodal-release profile does not alone establish infringement. The analysis must identify the particle architecture, coating chemistry, drug location, timing profile, and any relevant product-specific patents. How does US 5,837,284 compare with Concerta and other methylphenidate patents?US 5,837,284 is directed to multiparticulate or layered particles. Concerta uses an osmotic-controlled oral delivery system with a tablet core and semipermeable membrane. The two patent landscapes therefore differ materially.
A product can avoid the 5,837,284 claim set while still infringing a separate patent estate directed to a different release mechanism. How strong is the patent estate for US 5,837,284?The patent was commercially meaningful while in force because the independent claims captured the central bimodal-release architecture. Its strength varied by claim type.
Potential validity issues would have centered on anticipation, obviousness, written description, enablement, and indefiniteness. The most important prior-art questions would have been whether earlier references disclosed:
Because the patent has expired, these validity issues have limited present commercial significance except for historical litigation analysis, freedom-to-operate opinions concerning past conduct, and prosecution strategy for related patent families. What manufacturing and intellectual-property barriers remain?The expired patent does not prevent manufacture of the claimed dosage form. Technical barriers may remain, including:
A generic manufacturer must also establish pharmaceutical equivalence and bioequivalence under FDA requirements. For an extended-release product, FDA may require comparative pharmacokinetic testing under fasting, fed, and other applicable conditions. (FDA, 2024b) Later patents may cover particular coating processes, excipient combinations, particle-size distributions, dosage strengths, or release specifications. Those patents require a separate family-level review and are not revived by US 5,837,284. What are the generic launch scenarios?The main launch scenarios are:
The highest residual risk would arise from later patents covering the same commercial product or from manufacturing and method-of-use claims that are independent of the expired patent. Key Takeaways
FAQs About US Patent 5,837,284Does US Patent 5,837,284 still block generic methylphenidate?No. The patent expired in 2016. Any current generic barrier must arise from other patents, regulatory exclusivity, or non-patent regulatory requirements. Does the patent cover all extended-release methylphenidate capsules?No. It covers dosage forms with defined immediate and delayed release characteristics and specific particle or coating limitations. Continuous-release products and different delivery systems may fall outside the claims. Does a product need to use d-threo-methylphenidate to infringe?No. Claims 1 and 23 are not limited to d-threo-methylphenidate. Claims 27 through 29 are specifically directed to d-threo-methylphenidate or its pharmaceutically acceptable salts. Does using a different coating polymer avoid the patent?It may avoid narrower claims directed to specified ammonio methacrylate compositions, ratios, or fillers. It may not avoid a broader claim if the alternative coating falls within the claim construction of "ammonio methacrylate copolymer" and produces the required delayed dose. Is Ritalin LA protected only by US Patent 5,837,284?No. A commercial product can be associated with multiple patents, patent applications, regulatory protections, trademarks, and manufacturing rights. The expiration of 5,837,284 does not establish that every other Ritalin LA-related right has expired. References
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Drugs Protected by US Patent 5,837,284
| 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 |
International Family Members for US Patent 5,837,284
| Country | Patent Number | Estimated Expiration | Supplementary Protection Certificate | SPC Country | SPC Expiration |
|---|---|---|---|---|---|
| Austria | 306266 | ⤷ Start Trial | |||
| Austria | 368458 | ⤷ Start Trial | |||
| Australia | 2002318302 | ⤷ Start Trial | |||
| Australia | 738521 | ⤷ Start Trial | |||
| >Country | >Patent Number | >Estimated Expiration | >Supplementary Protection Certificate | >SPC Country | >SPC Expiration |
