US Patent 6,358,527: Scope, Claim Construction, Expiration, and Galantamine Patent Landscape

US Patent 6,358,527 covers a specific fast-dissolving oral tablet containing galantamine hydrobromide and a defined excipient system. Its claims are narrower than a basic galantamine composition patent because they require a spray-dried lactose monohydrate/microcrystalline cellulose diluent in a 75:25 ratio and an insoluble or poorly soluble cross-linked polymer disintegrant.

The patent’s US statutory term has expired. The claims therefore do not currently block generic manufacture, sale, or use in the United States, subject to separate patent rights and regulatory requirements.

What does US Patent 6,358,527 cover?

US 6,358,527 covers two related subject matters:

Methods of treating dementia, mania, or nicotine dependence with a specified galantamine hydrobromide tablet.
A fast-dissolving galantamine hydrobromide tablet made using a specified dry-blending and compression process.

The patent is directed to the formulation and manufacture of the tablet, not to galantamine as a molecule or to every pharmaceutical use of galantamine.

Element	Required by the independent claims
Active ingredient	Galantamine hydrobromide in a 1:1 salt form
Dosage form	Tablet
Therapeutic claims	Dementia, mania, or nicotine dependence
Diluent	Spray-dried mixture of lactose monohydrate and microcrystalline cellulose
Diluent ratio	75:25
Disintegrant	Insoluble or poorly soluble cross-linked polymer
Manufacturing process	Dry blending, optional lubricant addition, dry compression, optional film coating
Claimed performance	Fast dissolution, expressly recited in claim 6

The 1:1 designation identifies the stoichiometric relationship between galantamine and hydrobromide in the salt. It does not describe a 1:1 mixture of active ingredient and excipient.

What are the independent claims in US 6,358,527?

Claim 1: treatment method

Claim 1 requires administering a tablet that contains:

a therapeutically effective amount of galantamine hydrobromide;
a pharmaceutically acceptable carrier;
a spray-dried lactose monohydrate/microcrystalline cellulose diluent at 75:25; and
an insoluble or poorly soluble cross-linked polymer disintegrant.

The claim is a combination claim. Every listed formulation limitation must be present for literal infringement. A tablet containing galantamine hydrobromide but using a different diluent, a different ratio, or a non-cross-linked disintegrant would not literally satisfy claim 1.

The claim also requires treatment of one of the three listed conditions. A product with the same formulation but marketed only for an unlisted indication would raise different infringement issues from a product labeled for dementia, mania, or nicotine dependence.

Claim 6: fast-dissolving tablet and manufacturing sequence

Claim 6 requires a tablet made by a defined manufacturing sequence:

Dry blending galantamine hydrobromide, the cross-linked polymer disintegrant, and an optional glidant with the 75:25 spray-dried diluent.
Optionally adding a lubricant.
Compressing the blend in the dry state.
Optionally film-coating the resulting tablet.

The claim excludes wet granulation as the recited manufacturing route. The optional steps do not narrow the claim when omitted. A lubricant and film coating may be absent while the claim remains satisfied.

The claim is commercially important because it focuses on direct compression or a substantially dry-compression process. The formulation is designed to avoid a more complex granulation process while maintaining rapid tablet disintegration and dissolution.

How do dependent claims 2 through 5 narrow the patent?

Claims 2 through 5 depend from claim 1 and narrow the covered treatment indication.

Claim	Added limitation
Claim 2	The disorder is dementia
Claim 3	The dementia is Alzheimer’s dementia
Claim 4	The disorder is mania
Claim 5	The disorder is nicotine dependence

Claim 3 is the most commercially relevant dependent claim because galantamine’s principal approved use is the treatment of mild-to-moderate Alzheimer’s dementia. Claims 4 and 5 cover uses that are broader in the claim language but do not correspond to the principal US approved indication for the marketed galantamine products.

A dependent claim incorporates all limitations of the parent claim. Thus, claim 3 requires the full formulation specified in claim 1, not merely galantamine treatment for Alzheimer’s dementia.

What formulation is protected by US 6,358,527?

The formulation protection depends on the combination of excipients rather than on a single ingredient.

Spray-dried lactose and microcrystalline cellulose

The diluent must comprise a spray-dried mixture of:

75% lactose monohydrate; and
25% microcrystalline cellulose.

The wording identifies both the composition and the physical preparation of the diluent. A simple physical blend of separately sourced lactose and microcrystalline cellulose may not satisfy the “spray-dried mixture” limitation.

The 75:25 ratio is a material limitation. A formulation using a 70:30 or 80:20 mixture would present a substantial non-infringement argument, although the result would depend on claim construction, measurement conventions, and any applicable doctrine-of-equivalents analysis.

Cross-linked polymer disintegrant

The claims require an insoluble or poorly soluble cross-linked polymer disintegrant. Typical excipient candidates in this category include crospovidone, croscarmellose sodium, and sodium starch glycolate, although the specific patent specification and prosecution history control how broadly the term is construed.

The disintegrant requirement is separate from the diluent requirement. A formulation using the correct 75:25 spray-dried diluent but a soluble, non-cross-linked disintegrant would not satisfy the claim as written.

Galantamine hydrobromide

The claims do not cover all galantamine salts. They specifically require galantamine hydrobromide in a 1:1 form. A formulation using galantamine free base, a different acid-addition salt, or a different stoichiometric form would fall outside the literal active-ingredient limitation.

What manufacturing process is protected by claim 6?

Claim 6 is directed to a dry-state compression process. Its principal process limitations are:

dry blending;
optional glidant incorporation;
optional lubricant incorporation;
compression in the dry state; and
optional film coating.

The claim does not require a particular tablet weight, strength, dissolution time, coating composition, or dosage strength in the text supplied. Those parameters could be present in the specification or prosecution history, but they cannot be added to the claim without a basis in the intrinsic record.

A manufacturer using wet granulation, roller compaction, fluid-bed granulation, or another process would have a potential non-infringement position against the process language of claim 6. That position would not necessarily defeat claim 1 if the resulting tablet were administered for a claimed condition and contained all of claim 1’s formulation elements.

Is US Patent 6,358,527 still enforceable?

No. US Patent 6,358,527 has expired under the ordinary US patent term framework.

Event	Approximate status
US patent issued	March 19, 2002
Patent term basis	20 years from the relevant nonprovisional filing or priority framework
Statutory expiration	2019
Current enforceability	Expired
Current blocking effect	None from this patent alone

The exact expiration date should be taken from the USPTO patent-term record and the FDA Orange Book historical listing. Patent expiration eliminates enforceability for future conduct but does not erase rights relating to infringement that occurred before expiration, subject to applicable limitations periods and litigation facts.

The patent’s expiration means a generic sponsor no longer needs to overcome this patent through a current Paragraph IV certification. A historical Paragraph IV challenge may still be relevant to past market entry, settlement history, or damages analysis.

What was the FDA and Orange Book status of this patent?

Galantamine hydrobromide was marketed in the United States under the Reminyl brand, later renamed Razadyne. The FDA-approved product is an oral immediate-release tablet and also has other approved dosage forms, including extended-release capsules and oral solution.

The relevant FDA product history includes:

FDA matter	Status
Active ingredient	Galantamine hydrobromide
Brand	Reminyl, later Razadyne
Principal indication	Mild-to-moderate Alzheimer’s dementia
NDA sponsor	Janssen-related product sponsor
Regulatory pathway	NDA for the branded product; ANDA pathway for generics
Orange Book role	Historical listing of patent information associated with the reference product
Current effect of US 6,358,527	Expired patent, no current exclusivity barrier

The patent did not create molecular exclusivity for galantamine. It was a formulation and use patent associated with the branded product. FDA approval of generic galantamine products can proceed through the ANDA pathway once applicable patents and regulatory exclusivities no longer block approval.

When did galantamine lose US exclusivity?

Galantamine’s primary market protection ended through a combination of patent expiry and generic competition.

The relevant distinction is between:

active-ingredient exclusivity;
formulation patents;
method-of-use patents;
FDA regulatory exclusivity; and
commercial availability of generic products.

Galantamine is a small molecule, so biosimilar rules do not apply. Generic manufacturers file ANDAs with Paragraph I, II, III, or IV certifications against Orange Book-listed patents. Once the relevant patent protection expired or was otherwise resolved, generic entry became possible.

US 6,358,527 no longer supports a delayed generic launch. Any current market protection would have to arise from another unexpired patent, a separate regulatory exclusivity period, a formulation-specific right, or a non-patent commercial factor.

Were Paragraph IV challenges or patent litigation associated with this patent?

A Paragraph IV certification is an ANDA applicant’s assertion that an Orange Book-listed patent is invalid, unenforceable, or will not be infringed. The supplied claim text does not establish the identity of any challenger, filing date, district court action, settlement agreement, or launch date.

The practical litigation position is now different because the patent has expired. A current Paragraph IV dispute directed solely to US 6,358,527 would generally have no prospective exclusionary value. Historical litigation can still matter for:

damages for pre-expiration sales;
launch timing;
180-day generic exclusivity;
settlement consideration;
covenant-not-to-sue terms; and
evidence concerning claim construction.

No biosimilar litigation analysis is relevant to galantamine because the product is a conventional small-molecule drug.

How strong was the patent estate?

Strengths

The patent had meaningful narrowing limitations:

specified galantamine hydrobromide salt;
a defined 75:25 excipient ratio;
spray-dried diluent preparation;
cross-linked polymer disintegrant;
dry compression process;
treatment indication limitations.

These limitations could make design-around possible, but they also gave the patent a technically defined formulation target. A generic product using a different excipient system or manufacturing process could avoid literal infringement.

Weaknesses

The same limitations narrowed the patent’s commercial reach:

it did not cover galantamine generally;
it did not cover all salts of galantamine;
it did not cover every oral dosage form;
it did not cover extended-release products unless they independently met the claimed limitations;
it did not cover every method of treating Alzheimer’s disease;
it expired in 2019.

The patent therefore had stronger value as a historical branded-tablet formulation patent than as a durable barrier to all generic galantamine products.

How does this patent compare with broader galantamine rights?

Right type	Scope relative to US 6,358,527	Current commercial significance
Compound patent	Covers galantamine or a chemical form broadly	Likely expired before or around the branded product’s mature lifecycle
Method-of-use patent	Covers treatment of a defined disease	May have affected labeling or ANDA certifications
Formulation patent	Covers excipients, dosage form, release profile, or manufacturing	US 6,358,527 is in this category
Extended-release patent	Covers once-daily or modified-release galantamine	Separate analysis required
Manufacturing patent	Covers synthesis, purification, crystallization, or salt formation	Could affect API sourcing
Regulatory exclusivity	FDA-created, time-limited protection	Separate from patent enforceability

US 6,358,527 should not be treated as a complete galantamine freedom-to-operate opinion. A commercial assessment must separate tablet formulation rights from extended-release formulation rights, API manufacturing patents, use patents, and foreign equivalents.

What generic launch risks remain?

The patent itself presents no current launch risk because it is expired. Residual risk can arise from other sources:

An unexpired patent covering extended-release galantamine.
A separate formulation patent covering a specific dosage strength or dissolution profile.
API process patents held by a supplier.
A patent covering a particular indication or labeling strategy.
Trade-secret restrictions involving manufacturing know-how.
FDA requirements for bioequivalence, dissolution, impurities, stability, and product quality.

A generic applicant using the same 75:25 spray-dried diluent and cross-linked polymer disintegrant would not face an enforceable claim from US 6,358,527 alone. The formulation could still implicate another patent family if the same composition appears in a later patent.

Key Takeaways

US 6,358,527 is a formulation and treatment patent for fast-dissolving galantamine hydrobromide tablets.
The central formulation limitation is a spray-dried 75:25 lactose monohydrate/microcrystalline cellulose diluent combined with an insoluble or poorly soluble cross-linked polymer disintegrant.
Claim 1 covers treatment of dementia, mania, or nicotine dependence with the defined tablet.
Claim 3 narrows the method to Alzheimer’s dementia.
Claim 6 covers a dry-blending, dry-compression manufacturing sequence with optional lubrication and film coating.
The patent does not cover galantamine generally, every galantamine salt, or every galantamine dosage form.
The US patent expired in 2019 and is not a current barrier to generic galantamine entry.
Galantamine is a small molecule, so biosimilar risk is not applicable.
Current freedom-to-operate analysis must review separate formulation, extended-release, method-of-use, API, and foreign patent families.

FAQs

Does US 6,358,527 cover Razadyne ER?

Not by its supplied claims alone. Claim 6 is directed to a fast-dissolving tablet, while Razadyne ER is an extended-release capsule product. Any extended-release coverage must be assessed under separate patent claims.

Can a generic use crospovidone after this patent expired?

Yes, US 6,358,527 no longer prevents use of crospovidone or the claimed excipient combination. A separate unexpired patent could still affect a particular formulation.

Does the 75:25 lactose-to-cellulose ratio have to be exact?

The claim recites a 75:25 ratio. Literal infringement analysis would require determining how the ratio is measured and whether manufacturing tolerances are covered. The patent’s expiration makes that issue primarily historical.

Does a different galantamine salt avoid the claims?

Generally, yes, for literal infringement of the supplied claims, because they require galantamine hydrobromide in a 1:1 form. A different salt could implicate separate patents or regulatory issues.

Is a current Paragraph IV certification needed for US 6,358,527?

No current Paragraph IV certification is needed solely because of this expired patent. The applicant must evaluate all patents listed for the applicable reference product and certify as required under the ANDA framework.

References

U.S. Patent No. 6,358,527. (2002). Pharmaceutical compositions comprising galanthamine. U.S. Patent and Trademark Office.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations. Center for Drug Evaluation and Research.
U.S. Food and Drug Administration. (n.d.). Orange Book: Approved drug products with therapeutic equivalence evaluations. Center for Drug Evaluation and Research.
U.S. Food and Drug Administration. (n.d.). Abbreviated new drug application submissions. Center for Drug Evaluation and Research.
U.S. Patent and Trademark Office. (n.d.). Patent term adjustment and patent term expiration information. U.S. Department of Commerce.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
	96201676	Jun 14, 1996

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	008237	⤷ Start Trial
Argentina	070670	⤷ Start Trial
Austria	285777	⤷ Start Trial
Australia	3174397	⤷ Start Trial
Australia	726212	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 6,358,527

Summary for Patent: 6,358,527