Details for Patent: 4,579,855
Summary for Patent: 4,579,855
| Title: | Melfloquin hydrochloride | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Abstract: | Mefloquin hydrochloride in the form of modification E as characterized by IR spectrum and X-ray diffraction pattern, as well as a process for the preparation thereof by treating mefloquin hydrochloride, comprising at least partially another modification, that is, mefloquin hydrochloride which is not pure mefloquin hydrochloride in the form of modification E, with methanol and/or ethanol, in the presence of less than 30 volume/percent of water. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inventor(s): | Helmut Bomches, Bruno Hardegger | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Assignee: | F Hoffmann La Roche AG , Hoffmann La Roche Inc | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Application Number: | US06/655,813 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Patent Claim Types: see list of patent claims | Use; Composition; | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Patent landscape, scope, and claims: | United States Patent 4,579,855: Mefloquine Hydrochloride Modification E Patent Scope and LandscapeUS Patent 4,579,855 protected a crystalline polymorph of mefloquine hydrochloride, identified as modification E, together with dry pharmaceutical compositions and antimalarial treatment methods using that solid form. The patent issued to Hoffmann-La Roche Inc. in 1986 and expired in 2003 under the pre-URAA 17-year term measured from issuance. It no longer creates an enforceable barrier to generic mefloquine hydrochloride products. The patent was important because it did not claim mefloquine hydrochloride as a molecule in all forms. Its central limitation was the specific solid-state form, modification E, and products or uses containing that form. What does US Patent 4,579,855 cover?US 4,579,855 covers four related categories:
The patented compound is the hydrochloride salt of mefloquine, also described chemically as erythro-alpha-2-piperidyl-2,8-bis-(trifluoromethyl)-4-quinolinemethanol hydrochloride. The patent does not broadly cover:
The patent record identifies the invention as a new crystalline form of mefloquine hydrochloride and assigns it to Hoffmann-La Roche Inc. (USPTO, 1986; Google Patents, n.d.). What are the claims of US 4,579,855?
Claims 1 and 2 are product claims. Claims 3 and 4 are composition claims. Claims 5 and 6 are method-of-use claims. How broad is claim 1 for mefloquine modification E?Claim 1 is directed to the substance itself, but only when the substance is both:
The claim therefore has narrower scope than a claim to mefloquine hydrochloride without a polymorph limitation. A competing manufacturer using a different polymorph, an amorphous form, or a material not meeting the “essentially pure” and modification E limitations would have a stronger non-infringement position. The phrase “essentially pure” is significant. The patent does not state a single numerical purity threshold in the claim text supplied. In an infringement dispute, the analysis would likely focus on:
Claim 1 is not limited to a particular tablet strength, dosage, excipient, country of manufacture, or indication. What does claim 2 add to the modification E protection?Claim 2 defines the same crystalline form through analytical characteristics. It refers to:
This claim gives the patent holder a product-identification route independent of a chemical name alone. A batch could be evaluated by powder X-ray diffraction and infrared spectroscopy to determine whether its solid-state structure corresponds to modification E. The “and/or” wording increases the potential breadth of the characterization language, but the claim remains dependent on correspondence to the patented form. A minor difference in crystallinity, preferred orientation, instrument conditions, hydration state, or sample preparation would not automatically establish non-infringement. Conversely, an accused product would not necessarily avoid the claim merely because its manufacturer uses a different trade name or manufacturing process. What evidence would be relevant to a polymorph infringement analysis?A technical comparison would typically examine:
The patent’s Figures 5 and 6 are central claim-construction and testing references. They provide the reference characteristics for the claimed form. What pharmaceutical formulations are protected?Claim 3 protects a non-liquid, dry pharmaceutical composition containing:
The claim can cover tablets, capsules, powders, granules, or similar solid dosage forms if they contain the claimed polymorph and satisfy the dry, non-liquid limitation. The claim does not expressly require a particular excipient. An inert carrier could include conventional pharmaceutical carriers used to formulate solid oral dosage forms. The claim also does not require a particular dose, release profile, coating, tablet shape, or manufacturing method. The dry-form limitation is material. A liquid suspension, solution, injectable preparation, or other liquid dosage form would not fall within claim 3 as written, even if it originated from modification E, unless another claim or infringement theory applied. Does the patent protect the mefloquine, sulfadoxine, and pyrimethamine combination?Yes. Claims 4 and 6 specifically address the combination of:
Claim 4 covers the dry composition. Claim 6 covers administering that combination to treat or prevent malaria. These claims are narrower than claims 3 and 5 because they require both sulfadoxine and pyrimethamine. They could be relevant to a fixed-dose combination product, a co-packaged regimen, or a composition containing all three active ingredients, depending on the claim construction and product presentation. The claims do not broadly cover every mefloquine combination. A product containing mefloquine modification E and a different antimalarial, without sulfadoxine and pyrimethamine, would generally be analyzed under claim 3 or claim 5 rather than claims 4 or 6. What malaria uses are covered by claims 5 and 6?Claim 5 covers administration for treating or preventing “all forms of malaria” in a host in need of treatment. The claim permits modification E to be used alone or with other therapeutically active substances. The method claim is broad as to the malaria form and combination partner, but it remains limited by the requirement that the administered pharmaceutical composition contain mefloquine hydrochloride modification E in an antimalarially effective amount. Claim 6 is more specific. It requires the three-drug combination of modification E, sulfadoxine, and pyrimethamine. The method claims do not create a general monopoly over:
When did US Patent 4,579,855 expire?
US 4,579,855 was issued before the 1995 change to a 20-year term measured from the earliest effective nonprovisional filing date. The patent therefore falls under the older 17-year-from-issuance framework, subject to any terminal disclaimer or unusual term adjustment shown in the official file. Public patent databases report the patent as expired (USPTO, 1986; Google Patents, n.d.). The patent’s expiration eliminates current infringement liability under claims 1 through 6. A historical infringement analysis could still matter for activity conducted before expiration, subject to applicable limitation periods, patent-term records, and litigation-specific facts. What was the Orange Book status of the mefloquine patent?The relevant marketed product was Lariam, a mefloquine hydrochloride product associated with Roche’s US regulatory approvals. FDA Orange Book listings are product-specific and depend on the NDA, dosage form, patent submission, and the patent’s active status. Because US 4,579,855 expired in 2003, it is not a current enforceable Orange Book barrier to approval or marketing of generic mefloquine hydrochloride tablets. An expired patent may remain visible in historical regulatory or patent records, but it does not support a current 30-month stay or an enforceable Paragraph IV exclusion period. FDA approval of a generic mefloquine product would remain subject to ordinary requirements involving pharmaceutical equivalence, bioequivalence, labeling, quality, manufacturing, and any applicable exclusivity. The expired polymorph patent does not prevent a generic applicant from relying on an abbreviated new drug application pathway if the product satisfies FDA requirements (FDA, n.d.-a). Were there Paragraph IV challenges or patent litigation?No current Paragraph IV risk arises from US 4,579,855 because the patent expired more than two decades ago. A Paragraph IV certification is designed for an unexpired listed patent. It cannot create a continuing patent block after expiration. The patent also does not create a present litigation risk for:
A historical litigation review would require docket-level analysis of the original patent, related mefloquine patents, and any Hatch-Waxman disputes involving Lariam or generic mefloquine. The existence of US 4,579,855 alone does not establish that a Paragraph IV case occurred. What other patents formed the mefloquine patent landscape?The mefloquine estate was broader than US 4,579,855. It included several potential patent categories:
The key legal distinction is that a later patent could have covered a new formulation, dosage regimen, manufacturing process, or combination even after US 4,579,855 expired. Such a patent would not revive the expired modification E claims. It would require independent validity, enforceability, and claim coverage. Does mefloquine have biosimilar risk?No. Mefloquine is a chemically synthesized small-molecule drug, not a biologic. Biosimilar approval under the Public Health Service Act is therefore not the relevant pathway. The competitive threat is generic substitution through the ANDA pathway. Generic applicants would typically address:
The absence of biosimilar risk does not eliminate formulation or process patent issues, but those issues are separate from biologic exclusivity. How strong is the patent estate today?The enforceable strength of US 4,579,855 is zero because the patent has expired. Its historical technical scope was meaningful because the core product claim targeted a specific crystalline form that could be used in solid oral formulations. Its current commercial value is limited to:
The patent was stronger against a manufacturer that deliberately produced modification E in substantially pure form than against one using another polymorph or an amorphous material. Claims 3 through 6 created additional exposure where the patented form was placed in dry compositions or used in malaria treatment. Those claims did not extend beyond the modification E limitation. What generic launch scenarios exist?
A company evaluating launch risk should treat the patent as a historical reference, not as a current blocking right. The relevant present risks are regulatory compliance, supply-chain quality, trademark and labeling issues, and any later unexpired patents unrelated to US 4,579,855. What is the geographic coverage of this patent?US 4,579,855 covers only conduct within the territorial scope of the United States patent system. It does not directly control:
Related foreign applications or counterpart patents may have existed, but their scope, prosecution history, and expiration dates had to be assessed separately. A US expiration date does not establish expiration of a foreign counterpart. What manufacturing and IP barriers remain?The expired polymorph patent no longer creates a patent barrier. Operational barriers can remain in:
A manufacturer can select a different polymorph to avoid unnecessary dependence on the historical modification E process, but it still must show that the resulting product meets regulatory specifications and performs acceptably. Key Takeaways
Frequently Asked QuestionsCan a generic manufacturer use mefloquine hydrochloride modification E today?Yes. US 4,579,855 is expired, so its modification E claims are no longer enforceable in the United States. Did US 4,579,855 claim Lariam by brand name?No. The claims are directed to mefloquine hydrochloride modification E, pharmaceutical compositions, and treatment methods. They do not depend on the Lariam trademark. Does the patent cover mefloquine free base?No. The claims recite mefloquine hydrochloride, the hydrochloride salt form. Mefloquine free base is not within the literal compound language supplied. Could a later patent still block a mefloquine product?Yes. A later unexpired patent could cover a specific formulation, dosage regimen, manufacturing method, combination, or delivery system. That would be a separate right from US 4,579,855. Is modification E required for every FDA-approved mefloquine tablet?The patent claims required modification E, but FDA approval requirements are separate. An approved product must meet the applicable regulatory specifications and reference-product requirements; the expired patent no longer dictates commercial manufacture. References
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Drugs Protected by US Patent 4,579,855
| 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: 4,579,855
| Foriegn Application Priority Data | ||
| Foreign Country | Foreign Patent Number | Foreign Patent Date |
| Switzerland | 5459/83 | Oct 07, 1983 |
International Family Members for US Patent 4,579,855
| Country | Patent Number | Estimated Expiration | Supplementary Protection Certificate | SPC Country | SPC Expiration |
|---|---|---|---|---|---|
| Austria | 55387 | ⤷ Start Trial | |||
| Bulgaria | 60836 | ⤷ Start Trial | |||
| Germany | 3482926 | ⤷ Start Trial | |||
| European Patent Office | 0137375 | ⤷ Start Trial | |||
| Japan | H0255432 | ⤷ Start Trial | |||
| Japan | S60105675 | ⤷ Start Trial | |||
| >Country | >Patent Number | >Estimated Expiration | >Supplementary Protection Certificate | >SPC Country | >SPC Expiration |
