Details for Patent: 4,820,738
Summary for Patent: 4,820,738
| Title: | 1,4-bis(substituted-amino)-5,8-dihydroxy-anthraquinones and leuco bases thereof | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Abstract: | This disclosure describes symmetrical 1,4-bis(substituted-amino)-5,8-dihydroxyanthraquinones useful as chelating agents and for inducing regression and/or palliation of cancer diseases in mammals. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inventor(s): | Keith C. Murdock, Frederick E. Durr | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Assignee: | Immunex Corp | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Application Number: | US06/823,265 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Patent Claim Types: see list of patent claims | Use; | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Patent landscape, scope, and claims: | United States Patent 4,820,738: Scope, Claims, Expiration, and Mitoxantrone Patent LandscapeU.S. Patent No. 4,820,738 is a method-of-use patent covering the administration of specified 1,4-bis(aminoalkylamino)-5,8-dihydroxyanthraquinone compounds, their leuco bases, tautomers, and pharmacologically acceptable acid-addition salts for treating solid tumors and leukemia. The claims principally encompass mitoxantrone-related anthracenedione compounds, including the dihydrochloride salt of mitoxantrone. The patent issued in 1989 and, under the pre-1995 patent-term regime, expired no later than 2006, absent an unusual term adjustment or restoration. It therefore does not currently block generic mitoxantrone manufacture, sale, or use in the United States. Its historical importance is greater than its present exclusionary value. What compounds does U.S. Patent 4,820,738 cover?The patent covers a chemical genus defined by anthraquinone or anthracene-dione structures bearing aminoalkylamino substituents and hydroxyl groups. The claims include:
The most commercially relevant compound is mitoxantrone, generally identified as mitoxantrone hydrochloride or mitoxantrone dihydrochloride. Its chemical description is commonly given as 1,4-dihydroxy-5,8-bis[[2-[(2-hydroxyethyl)amino]ethyl]amino]-9,10-anthracenedione dihydrochloride. The claim language uses a different but structurally corresponding numbering and nomenclature convention. What is the central chemical limitation?The central structural limitation is the presence of two aminoalkylamino substituents on the anthraquinone or anthracenedione nucleus, together with hydroxyl substitution and defined terminal nitrogen groups. Claim 1 covers compounds selected from a Markush group in which:
The supplied claim text does not reproduce the chemical drawings for every Q alternative. The full scope of those alternatives must therefore be read from the issued patent drawings and specification, not from the text-only transcription. What do the individual claims cover?
Claims 1 and 4 are the principal genus claims. Claims 2 through 12 add structural, disease, compound, or animal-model limitations. What is the claim scope for solid tumors?Claim 1 requires four principal elements:
The solid tumor must be susceptible to growth inhibition by the administered compound. That final limitation is functional. It does not identify a closed list of tumor types, but it requires that the treatment be directed to a tumor responsive to the compound. Claim 1 does not require:
Claim 3 provides narrower coverage for six specified compounds, including the dimethylaminoethyl, diethylaminoethyl, hydroxyethylaminoethyl, and aminoethyl analogues. What is the claim scope for leukemia?Claim 4 is directed to inducing regression of leukemia cell growth rather than merely inhibiting growth of solid tumors. The claim uses the same compound genus and substantially the same structural definitions as claim 1. The distinction between claims 1 and 4 is functional and disease-based:
Claim 6 specifically covers the aminoethyl compound or its dihydrochloride salt. Claims 7 through 11 identify additional dimethylaminoethyl and diethylaminoethyl compounds, including their leuco and oxidized forms. Claim 12 is limited to mice. It has primarily historical research significance and does not extend to human treatment unless another claim is independently satisfied. Does the patent cover mitoxantrone?Yes, the patent claims encompass mitoxantrone-related structures, including the dihydrochloride salt identified in claim 3(e). The patent’s nomenclature places the hydroxyl and aminoalkylamino groups at positions described as 5,8 and 1,4, while modern references commonly describe mitoxantrone using the corresponding anthracene-9,10-dione nomenclature. The relevant commercial substance is mitoxantrone hydrochloride. The FDA approved mitoxantrone injection for certain leukemia indications and later for worsening forms of multiple sclerosis. FDA labeling identifies mitoxantrone hydrochloride as the active ingredient and describes its anthracenedione chemical class.[2] The patent does not, however, claim every possible use of mitoxantrone. It claims only the treatment methods specified in the claims. A product claim, manufacturing claim, formulation claim, or unrelated method-of-use claim would require separate patent authority. What is the patent’s expiration date?The patent issued on April 11, 1989. Because it belongs to the pre-June 8, 1995 patent-term period, the ordinary term was generally 17 years from issuance rather than 20 years from the earliest nonprovisional filing date. The resulting ordinary expiration date was April 11, 2006.
Patent term restoration under the Hatch-Waxman Act could theoretically extend certain regulatory-review periods, but the available patent and product history does not establish a restoration that would preserve enforceability today. The patent is not a current barrier to generic entry. What is the Orange Book status of mitoxantrone?Mitoxantrone hydrochloride was approved through an NDA and was historically associated with the branded product Novantrone. The FDA Orange Book lists approved drug products, reference-listed drugs, patents, and exclusivity information. Any patent listed for the original mitoxantrone product does not revive an expired patent or create a current exclusionary right.[3] U.S. Patent 4,820,738 should be treated as expired for current Orange Book and generic-entry analysis. The relevant commercial question is whether any later, unexpired patents cover a particular generic product, formulation, manufacturing process, or use. This patent alone does not support a present Paragraph IV litigation position. Were there Paragraph IV challenges to this patent?A Paragraph IV certification is relevant only while a listed patent remains unexpired or otherwise carries a meaningful regulatory listing effect. Because U.S. Patent 4,820,738 expired in 2006, it is not a current basis for a Paragraph IV challenge. Generic mitoxantrone applicants could have challenged listed patents during the patent’s effective term by certifying that the patent was invalid, unenforceable, or would not be infringed. The supplied patent text does not establish a particular ANDA filer, notice letter, district-court complaint, settlement, or consent judgment involving this patent. No such event should be attributed to the patent without a docket or FDA listing record. The practical present-day position is:
What formulation patents protect mitoxantrone?U.S. Patent 4,820,738 is not a formulation patent. Its claims do not require:
The patent also does not claim a manufacturing process. A competitor could therefore avoid the patent, even during its term, by using a noninfringing process or formulation if the resulting method of treatment did not satisfy the claimed limitations. For present diligence, the relevant search categories are:
The expired method patent should not be conflated with later product-specific or formulation-specific rights. Does the patent cover multiple sclerosis treatment?Not expressly. The claims identify solid-tumor growth inhibition and leukemia-cell regression. They do not recite multiple sclerosis, autoimmune disease, neurological disease, relapse reduction, disability progression, or any other multiple-sclerosis endpoint. Mitoxantrone was later approved for worsening relapsing-remitting multiple sclerosis, progressive-relapsing multiple sclerosis, and secondary-progressive multiple sclerosis. That later indication is outside the express disease language of claims 1 through 12.[2] A later multiple-sclerosis patent could have been commercially important even though this patent did not claim that indication. The existence, scope, and expiration of any such later patent must be evaluated separately from U.S. Patent 4,820,738. How strong was the patent estate?Chemical scopeThe chemical scope was moderately broad because the patent included:
That breadth created potential coverage around several anthracenedione analogues rather than only one commercial molecule. Method scopeThe method claims were narrower than a compound claim. Each asserted case would require proof that:
Commercial strengthThe patent was commercially useful during the period when mitoxantrone was being developed and introduced. Its present strength is zero as an exclusionary right because it expired. Historical importance does not translate into current blocking power.
Which companies challenged or competed with mitoxantrone?Mitoxantrone competed principally with anthracycline and anthracenedione oncology products, including:
For generic mitoxantrone, competition came from ANDA applicants producing injectable mitoxantrone hydrochloride. Because mitoxantrone is a small-molecule drug, the relevant pathway is an ANDA, not a biosimilar application. The patent record supplied does not identify a specific settlement agreement, license, or litigation campaign involving U.S. Patent 4,820,738. No licensing transaction should be inferred merely from assignment or commercial marketing history. What is the biosimilar risk?There is no biosimilar issue for mitoxantrone. Mitoxantrone is a chemically synthesized small molecule regulated under the generic-drug pathway. Competitors generally seek approval through ANDAs demonstrating pharmaceutical equivalence and bioequivalence to the reference product. The appropriate competitive risks are:
U.S. Patent 4,820,738 does not create a current biosimilar or generic barrier. What generic launch risks exist?Current generic launch risk is principally commercial and regulatory rather than patent-based.
Mitoxantrone injection requires sterile manufacturing, quality control, validated container closure, and reliable supply of active pharmaceutical ingredient. Those factors can create practical barriers even when patent barriers have ended. What geographic coverage does the patent have?U.S. Patent 4,820,738 provides territorial rights only in the United States. It does not directly control:
Foreign counterparts may have been filed within the same patent family, but each jurisdiction requires an independent review of filing, grant, maintenance, term, opposition, and lapse data. The U.S. expiration date cannot be applied automatically to foreign family members. What patent litigation affects U.S. Patent 4,820,738?The supplied claim text does not identify litigation. The patent’s age and expiration materially reduce the likelihood of current infringement litigation. Any historical case would need to be verified through PACER, court opinions, USPTO records, FDA Orange Book history, or ANDA litigation databases. For current diligence, the patent should be classified as:
Key Takeaways
Frequently Asked QuestionsIs U.S. Patent 4,820,738 still enforceable?No. Its ordinary pre-1995 patent term ended in 2006, subject to confirmation of any exceptional term adjustment or restoration. Does U.S. Patent 4,820,738 claim mitoxantrone itself?No. Based on the supplied claims, it claims methods of using a compound genus that encompasses mitoxantrone-related compounds and salts. Can a generic manufacturer make mitoxantrone today without infringing this patent?Yes, this expired patent does not independently prevent manufacture, approval, or sale of generic mitoxantrone. Does the patent cover mitoxantrone for multiple sclerosis?No express claim covers multiple sclerosis. The claims address solid tumors and leukemia-cell regression. Is mitoxantrone subject to biosimilar competition?No. Mitoxantrone is a small-molecule drug. The relevant competitors are generic ANDA applicants, not biosimilar sponsors. References
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Drugs Protected by US Patent 4,820,738
| 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 4,820,738
| Country | Patent Number | Estimated Expiration | Supplementary Protection Certificate | SPC Country | SPC Expiration |
|---|---|---|---|---|---|
| Argentina | 225884 | ⤷ Start Trial | |||
| Austria | 359484 | ⤷ Start Trial | |||
| Austria | A590678 | ⤷ Start Trial | |||
| Australia | 3877678 | ⤷ Start Trial | |||
| Australia | 527103 | ⤷ Start Trial | |||
| >Country | >Patent Number | >Estimated Expiration | >Supplementary Protection Certificate | >SPC Country | >SPC Expiration |
