United States Patent 5,387,612: Rasagiline Parkinson’s Treatment Claims, Expiration, and Patent Landscape

U.S. Patent No. 5,387,612 covers the use of R(+)-N-propargyl-1-aminoindan, now known as rasagiline, or a pharmaceutically acceptable salt, to treat Parkinson’s disease. The patent also claims oral, rectal, transdermal, and parenteral administration and specified dosage ranges. It was issued on February 7, 1995, and its original patent term expired on February 7, 2012, absent any applicable term adjustment or extension. The claims are no longer enforceable as live U.S. patent rights. [1]

The patent remains commercially important because it is a foundational rasagiline method-of-use patent associated with Azilect, but it does not currently block generic rasagiline manufacture, approval, or sale.

What drug and therapeutic use does U.S. Patent 5,387,612 cover?

The patent covers rasagiline, the R(+) enantiomer of N-propargyl-1-aminoindan. Rasagiline is a selective monoamine oxidase-B inhibitor used in Parkinson’s disease, either as monotherapy or as adjunctive treatment with levodopa, depending on the approved product labeling. [2]

The core independent claim recites:

A method of treating a subject for Parkinson’s disease;
Administration of R(+)-N-propargyl-1-aminoindan or a pharmaceutically acceptable salt;
An amount effective to treat the subject;
A “consists essentially of” transition.

The claim is directed to therapeutic use, not to the chemical compound itself. It does not claim:

The synthesis of rasagiline;
A particular pharmaceutical composition;
A specific tablet, capsule, patch, injection, or excipient system;
A manufacturing process;
A diagnostic method;
A particular Parkinson’s disease stage;
A specific mechanism of action.

The claimed active ingredient corresponds to rasagiline free base and its pharmaceutically acceptable salts, including rasagiline mesylate used in commercial products.

What are the claims of U.S. Patent 5,387,612?

Claim	Scope
1	Treating Parkinson’s disease with rasagiline or a pharmaceutically acceptable salt in an effective amount
2	Claim 1 where administration is oral
3	Claim 1 where administration is rectal
4	Claim 1 where administration is transdermal
5	Oral, rectal, or transdermal administration at 2 to 20 mg per daily dosage unit
6	Oral, rectal, or transdermal administration at 5 to 10 mg per daily dosage unit
7	Claim 1 where administration is parenteral
8	Parenteral administration at 1 to 10 mg/mL per daily dosage unit
9	Parenteral administration at 2 to 5 mg/mL per daily dosage unit

Claims 2 through 9 are dependent claims. They cannot be infringed unless the elements of claim 1 are also satisfied.

How broad is the independent method claim?

Claim 1 is broad in therapeutic subject matter. It is not limited to a particular dosage, route, treatment duration, disease severity, formulation, or co-administered drug.

The principal limitations are the following:

The active ingredient must be the R(+) enantiomer of N-propargyl-1-aminoindan.
The active ingredient may be administered as the free compound or a pharmaceutically acceptable salt.
The purpose must be treatment of Parkinson’s disease.
The administered amount must be effective to treat the subject.
The method must satisfy the “consists essentially of” language.

The “consists essentially of” transition generally permits components that do not materially affect the basic and novel characteristics of the claimed method. It is narrower than “comprising” but broader than “consisting of.” In a product liability or patent dispute, the practical question would be whether additional active ingredients or treatment steps materially change the rasagiline-based Parkinson’s treatment method.

The claim is not restricted to rasagiline monotherapy. Co-administration with levodopa or other Parkinson’s medicines would not necessarily avoid the claim if rasagiline remains the treatment agent and the additional therapy does not materially alter the claimed method.

What formulations and routes are protected?

The patent claims administration routes rather than formulation architecture.

Oral formulations

The oral claims potentially cover tablets, capsules, orally disintegrating dosage forms, powders, solutions, and other oral dosage forms containing rasagiline or a pharmaceutically acceptable salt. Claims 5 and 6 add daily dosage ranges of 2 to 20 mg and 5 to 10 mg.

Azilect is marketed as an oral tablet containing rasagiline mesylate. The principal approved strengths are 0.5 mg and 1 mg of rasagiline once daily, depending on treatment context and labeling. [2] Those commercial doses are below the express 5 to 10 mg range in claim 6 and below the 2 to 20 mg range in claim 5. Claim construction would require careful analysis of whether the claimed “mg” refers to rasagiline base, salt weight, or dosage-unit content.

Rectal formulations

Claim 3 covers rectal administration. Claim 5 and claim 6 extend specified dosage ranges to rectal use.

The patent does not require a suppository, enema, gel, or a particular excipient system. The claim could reach different rectal dosage forms if they deliver rasagiline for Parkinson’s treatment.

Transdermal formulations

Claim 4 covers transdermal administration. The patent does not claim a specific patch structure, adhesive, reservoir, membrane, penetration enhancer, or release profile.

A later transdermal product could have its own formulation or device patents, but that would not revive or extend the expired method claims of Patent 5,387,612.

Parenteral formulations

Claims 7 through 9 cover parenteral administration. The stated ranges are 1 to 10 mg/mL per daily dosage unit and 2 to 5 mg/mL per daily dosage unit.

The drafting of claims 8 and 9 creates a potential interpretation issue because “mg per mL per daily dosage unit” combines concentration and daily dosage terminology. A dispute could involve whether the claim requires a concentration, a total daily amount, or both. The claims also do not identify a particular injectable route, carrier, pH, preservative, or container system.

When did U.S. Patent 5,387,612 expire?

Event	Date or status
Patent issued	February 7, 1995
Patent term applicable to pre-June 8, 1995 applications	Generally 17 years from grant
Base expiration date	February 7, 2012
Current enforceability	Expired
Current ability to block generic entry	None based on this patent

The patent predates the Uruguay Round Agreements Act transition to the current 20-year-from-earliest-effective-filing-date system. Its term therefore generally ran for 17 years from issuance, subject to any applicable adjustment, disclaimer, or extension. Public patent records identify the patent as expired. [1]

There is no basis to treat Patent 5,387,612 as a current Orange Book barrier to generic rasagiline entry.

What was the Orange Book status of rasagiline?

The relevant reference product is Azilect, approved by the FDA in 2006 for Parkinson’s disease. Teva Pharmaceuticals developed and commercialized Azilect. [2]

The FDA Orange Book historically listed patents associated with Azilect, including method-of-use, compound, and pharmaceutical-composition rights. Orange Book listings can include patents other than the patent that first established the product’s commercial protection. [3]

Patent 5,387,612 should be distinguished from later rasagiline patents that may have covered:

The rasagiline compound or particular salt;
Pharmaceutical compositions;
Tablet formulations;
Dosage regimens;
Manufacturing processes;
Solid-state or crystalline forms;
Other product-specific characteristics.

An Orange Book listing does not itself establish patent validity. It identifies patents submitted by the NDA holder or patent owner as potentially relevant to the approved drug.

Which companies challenged rasagiline patents?

Generic rasagiline applicants could challenge listed patents through Paragraph IV certifications under the Hatch-Waxman Act. A Paragraph IV certification asserts that a listed patent is invalid, unenforceable, or not infringed. [4]

The principal commercial dispute involved generic versions of Azilect and later-issued Teva or related patent rights, rather than only the expired claims of Patent 5,387,612. Public litigation records should be reviewed separately for each ANDA, patent number, defendant, settlement date, and launch restriction.

Because Patent 5,387,612 expired in 2012, a current ANDA applicant does not face an injunction based on that patent. Any historical Paragraph IV challenge directed to the patent became commercially moot when the patent expired, although earlier litigation could have affected launch timing.

What is the broader rasagiline patent landscape?

The rasagiline estate has several layers:

Patent layer	Commercial function	Status of Patent 5,387,612
Therapeutic method	Parkinson’s disease treatment	Expired
Compound protection	Rasagiline or a particular salt	Separate patent analysis required
Formulation protection	Tablets, excipients, release properties	Not claimed by the patent
Dosage regimen	Dose, titration, or combination use	Only limited dose claims appear here
Manufacturing protection	Synthesis, resolution, salt formation	Not claimed by the patent
Regulatory exclusivity	FDA NCE or other exclusivity	Separate from patent term
Orange Book protection	Listed NDA patents	Depends on each listed patent

Patent 5,387,612 is strongest as a foundational method-of-use right and weakest as a present-day commercial barrier because its term has ended. It does not provide continuing protection for later rasagiline formulations or manufacturing processes.

Does rasagiline have biosimilar risk?

No. Rasagiline is a chemically synthesized small-molecule drug, not a biologic. The relevant competitive pathway is an abbreviated new drug application, or ANDA, rather than a biosimilar application under the Public Health Service Act.

The key market risks are therefore:

Generic rasagiline tablets;
Alternative manufacturers of rasagiline mesylate;
Paragraph IV litigation involving later-listed patents;
Formulation or process patents that could affect a particular applicant;
Regulatory exclusivity or pediatric exclusivity, if applicable at the relevant historical date.

Patent 5,387,612 itself does not create current biosimilar or generic-entry risk because it is expired.

How strong is the patent estate based on Patent 5,387,612?

The patent has high historical breadth and low current blocking value.

Historical strength

The patent claimed the therapeutic use of the specific R(+) enantiomer across multiple routes of administration. At the time of grant, a method claim covering Parkinson’s treatment with rasagiline could provide broad commercial leverage over products using the active ingredient for that indication.

Technical limitations

The claims do not protect:

The compound as a chemical composition;
A specific salt;
An approved dose of 0.5 mg or 1 mg;
A particular tablet;
A manufacturing process;
A crystal form;
A pharmacokinetic profile;
Combination therapy as a separately defined regimen.

Current strength

The patent is legally expired. Its current value is historical and evidentiary. It may be relevant to:

Prior-art analysis;
Patent-family mapping;
Freedom-to-operate chronology;
Licensing history;
Litigation reconstruction;
Assessment of later rasagiline patent validity.

It does not support an infringement claim for post-expiration commercial activity.

What generic launch scenarios exist for rasagiline?

The practical launch scenarios are:

Immediate generic competition based on expired foundational patents, subject to any later unexpired patents.
Delayed launch caused by later-listed formulation, dosage, or process patents.
At-risk launch after Paragraph IV certification and litigation.
Settlement-based launch under an agreed date or license.
Authorized generic competition involving the brand manufacturer or its licensee.

The relevant diligence question is not whether Patent 5,387,612 remains blocking. It does not. The question is whether later patents listed for Azilect or related rasagiline products imposed any remaining restrictions during the intended launch period.

Key Takeaways

U.S. Patent 5,387,612 covers treating Parkinson’s disease with rasagiline or a pharmaceutically acceptable salt.
The patent claims oral, rectal, transdermal, and parenteral administration.
Dependent claims recite specified dosage ranges, including 2 to 20 mg and 5 to 10 mg per daily dosage unit.
The patent does not claim the rasagiline molecule, a specific salt, a tablet formulation, or a manufacturing process.
The patent issued on February 7, 1995, and its base term expired on February 7, 2012.
It is no longer an enforceable U.S. barrier to generic rasagiline entry.
Rasagiline is a small-molecule drug, so generic competition proceeds through the ANDA pathway, not biosimilar regulation.
Later rasagiline patents, not Patent 5,387,612, determined the final timing of commercial generic entry.
The patent has historical importance but no present blocking value.

FAQs

Does Patent 5,387,612 cover Azilect specifically?

Yes, its method claims read on the use of rasagiline, the active pharmaceutical ingredient in Azilect, for treating Parkinson’s disease. The patent does not claim the Azilect brand, tablet design, or full commercial formulation.

Does the patent cover rasagiline mesylate?

The claims cover R(+)-N-propargyl-1-aminoindan and a pharmaceutically acceptable salt. Rasagiline mesylate would generally fall within the salt language, subject to claim construction and the patent’s expired status.

Can a generic manufacturer rely on the expiration of Patent 5,387,612?

Yes. A generic applicant does not need to design around an expired patent. It must still address any other applicable patents listed for the reference product or relevant to the proposed product.

Are the rectal, transdermal, and injectable claims commercially significant?

They broadened the patent’s historical route coverage, but they had limited relevance to the principal commercial Azilect product, which is an oral tablet. They do not independently extend the patent term.

Does expiration eliminate all rasagiline intellectual-property risk?

No. Expiration eliminates the blocking effect of this patent only. Separate risks may arise from later patents covering formulations, dosage regimens, manufacturing methods, solid-state forms, or other product-specific features.

References

United States Patent and Trademark Office. (1995). U.S. Patent No. 5,387,612: Method for treating Parkinson’s disease.
U.S. Food and Drug Administration. (2006). Azilect (rasagiline mesylate) prescribing information.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book.
U.S. Food and Drug Administration. (n.d.). Guidance for industry: 180-day exclusivity under the Hatch-Waxman amendments.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Israel	92952	Jan 03, 1990

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0436492	⤷ Start Trial	91195	Luxembourg	⤷ Start Trial
European Patent Office	0436492	⤷ Start Trial	CA 2005 00040	Denmark	⤷ Start Trial
European Patent Office	0812190	⤷ Start Trial	91191	Luxembourg	⤷ Start Trial
European Patent Office	0812190	⤷ Start Trial	CA 2005 00039	Denmark	⤷ Start Trial
European Patent Office	0812190	⤷ Start Trial	300205	Netherlands	⤷ Start Trial
European Patent Office	0812190	⤷ Start Trial	SPC024/2005	Ireland	⤷ Start Trial
European Patent Office	0812190	⤷ Start Trial	05C0033	France	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,387,612

Summary for Patent: 5,387,612