Details for Patent: 5,532,415

Summary for Patent: 5,532,415

Title:	R-enantiomer of N-propargyl-1-aminoindan, salts, compositions and uses thereof
Abstract:	The subject invention provides R(+)-N-propargyl-1-aminoindan and pharmaceutically acceptable salts thereof, as well as pharmaceutical compositions containing same. The subject invention also provides methods of treating a subject afflicted with Parkinson's disease, a memory disorder, dementia, depression, hyperactive syndrome, an affective illness, a neurodegenerative disease, a neurotoxic injury, brain ischemia, a head trauma injury, a spinal trauma injury, schizophrenia, an attention deficit disorder, multiple sclerosis, or withdrawal symptoms, using R(+)-N-propargyl-1-aminoindan or the pharmaceutically acceptable salt of the subject invention. The subject invention further provides a method of preventing nerve damage in a subject. Finally, the subject invention provides methods of preparing R(+)-N-propargyl-1-aminoindan, a salt thereof, and racemic N-propargyl-1-aminoindan.
Inventor(s):	Moussa B. H. Youdim, John P. M. Finberg, Ruth Levy, Jeffrey Sterling, David Lerner, Tirtsah Berger-Paskin, Haim Yellin, Alex Veinberg
Assignee:	Teva Pharmaceutical Industries Ltd
Application Number:	US08/411,398
Patent Claim Types: see list of patent claims	Compound;

US Patent 5,532,415: Rasagiline Mesylate Claim Scope, Expiration, and Patent Landscape

US Patent 5,532,415 is the foundational composition-of-matter patent for rasagiline mesylate, the active pharmaceutical ingredient in Azilect. Its sole claim covers the mesylate salt of the R(+)-enantiomer of N-propargyl-1-aminoindan. The claim is chemically narrow but commercially significant because it covers the specific active ingredient rather than a formulation, dosage regimen, or manufacturing process.

The patent’s exclusivity has expired. Generic and follow-on products are therefore assessed primarily against later formulation, polymorph, method-of-use, regulatory, and manufacturing rights rather than against the original compound claim.

What does US Patent 5,532,415 claim?

The patent contains one substantive claim:

“The mesylate salt of R(+)-N-propargyl-1-aminoindan.”

This is a composition-of-matter claim directed to a defined salt of a defined stereoisomer.

Claim elements

Claim element	Required limitation	Scope
Core structure	N-propargyl-1-aminoindan	Requires the propargyl-substituted aminoindan structure
Stereochemistry	R(+) enantiomer	Excludes the S(-) enantiomer and racemic material as such
Salt form	Mesylate, also called methanesulfonate	Excludes the free base and other acid-addition salts
Claim type	Product claim	Does not expressly require a dosage form, route of administration, indication, or manufacturing step

R(+)-N-propargyl-1-aminoindan is rasagiline. The claimed mesylate is rasagiline mesylate.

What the claim does not expressly cover

The claim does not, on its face, separately claim:

• Rasagiline free base
• S(-)-N-propargyl-1-aminoindan
• Racemic N-propargyl-1-aminoindan
• Rasagiline hydrochloride, tartrate, sulfate, or another non-mesylate salt
• A tablet or capsule formulation
• A particular dose
• A Parkinson’s disease treatment method
• A specific manufacturing process
• A particular polymorph unless the claimed salt is interpreted to include that form under applicable claim-construction principles

The claim’s commercial reach came from its ability to cover the active pharmaceutical substance itself, including the substance when supplied for use in an approved product.

How broad is the scope of US Patent 5,532,415?

The claim is narrow in chemical identity but broad in product application. It is narrow because every limitation must be satisfied: the compound must have the specified aminoindan structure, the R(+) configuration, and the mesylate counterion.

It is commercially broad because a product containing rasagiline mesylate generally cannot avoid the claim by changing:

• Tablet excipients
• Tablet strength
• Packaging
• Manufacturing site
• Tablet coating
• Release mechanism, unless the active ingredient is changed
• The Parkinson’s disease indication

A generic manufacturer producing rasagiline mesylate during the patent term would have faced direct composition-of-matter infringement risk, regardless of whether its formulation differed from Azilect’s formulation.

Literal infringement analysis

A product would generally satisfy the claim if analytical testing establishes that it contains:

1. Rasagiline rather than another aminoindan derivative;
2. The R(+) stereoisomer;
3. Mesylate as the counterion.

The claim does not require a minimum purity, particular particle size, crystal form, dosage strength, or excipient system. Those features would generally be relevant only if a later patent separately claimed them.

Salt and stereochemistry issues

The stereochemical limitation is material. A product consisting only of the S(-) enantiomer would not literally meet the R(+) limitation. A racemate would also present a different claim-construction and infringement analysis because the claim identifies the R(+) enantiomer specifically.

The mesylate limitation is also material. A manufacturer that used rasagiline free base or a different salt could avoid literal infringement of claim 1, although conversion to mesylate during formulation, manufacture, storage, or use could create a different infringement question.

The claim does not require a specific crystal form. A later-developed polymorph of rasagiline mesylate could still fall within claim 1 if it remains the claimed chemical salt. A polymorph patent would therefore provide an additional layer of protection rather than necessarily replacing the composition claim.

When did US Patent 5,532,415 expire?

The patent issued on July 2, 1996. Because the application was filed under the pre-1995 patent-term regime, the ordinary term was calculated under the applicable transition rules, subject to patent-term adjustment, patent-term extension, terminal disclaimers, and regulatory-review extension.

Public FDA and patent records associate the patent with the Azilect regulatory exclusivity period and a February 2017 expiration date. The patent is no longer an enforceable barrier to commercial entry.

Event	Date or status
Patent issued	July 2, 1996
Patent type	Composition of matter
Covered active ingredient	Rasagiline mesylate
FDA product associated with the asset	Azilect
Regulatory approval of Azilect	May 2006
Patent status as of 2026	Expired
Commercial implication	No current blocking composition claim from US 5,532,415

The precise enforceability period should be distinguished from the base term because older US patents could receive patent-term extension for regulatory review. The relevant commercial conclusion is unchanged: US 5,532,415 no longer prevents a manufacturer from marketing rasagiline mesylate in the United States.

What was the FDA and Orange Book status of rasagiline mesylate?

Azilect, containing rasagiline mesylate, received FDA approval in 2006 for Parkinson’s disease. The product was approved as an oral tablet and was initially indicated for monotherapy and adjunctive therapy with levodopa.

The Orange Book historically listed patents associated with Azilect, including the original composition patent and later patents directed to additional aspects of rasagiline therapy. The original composition patent was the most fundamental right because it covered the active pharmaceutical ingredient itself.

FDA exclusivity

Azilect received five-year new chemical entity exclusivity. That period protected the approved active ingredient from an ANDA relying on the product’s approval during the statutory exclusivity period, subject to the Hatch-Waxman framework.

The FDA approval and exclusivity milestones were separate from the patent term:

Protection	Function	Status
NCE exclusivity	Regulatory protection for the new active ingredient	Expired
US 5,532,415	Composition patent for rasagiline mesylate	Expired
Later method/formulation patents	Potentially delayed or limited generic approval depending on listing and certification	Generally time-limited
Orange Book listing	Public notice of patents submitted for the reference product	Historical relevance after expiration

Which later patents affected rasagiline mesylate?

The rasagiline patent estate extended beyond US 5,532,415. Later patents and applications addressed therapeutic use, formulation, pharmaceutical compositions, and potentially solid-state or manufacturing characteristics.

A patent-landscape review should separate four categories:

1. The original compound patent;
2. Method-of-use patents;
3. Formulation and pharmaceutical-composition patents;
4. Process, salt, polymorph, and solid-state patents.

Method-of-use patents

Later rasagiline patents addressed treatment of Parkinson’s disease and related therapeutic uses. These claims could cover administering rasagiline at specified doses, using it with levodopa, or treating defined patient populations.

A method patent does not necessarily prevent all sale of rasagiline. Its practical effect depends on:

• Whether the patented indication appears in the generic label;
• Whether the FDA-approved label includes the patented use;
• Whether the patent was listed in the Orange Book;
• Whether a generic applicant submitted a Paragraph IV certification;
• Whether the patent was enforceable when the product launched.

A generic applicant can sometimes pursue a section viii statement, commonly called a skinny label, to omit a patented indication. That strategy is less useful when the patent claims all approved uses or when the remaining label still induces infringement.

Formulation patents

Formulation patents may claim:

• Specific excipients;
• Tablet composition;
• Stability characteristics;
• Dissolution profiles;
• Controlled-release delivery;
• Particle-size distributions;
• Specific salt or solid-state forms;
• Manufacturing parameters that produce a defined product.

A generic product using a different excipient system may avoid a formulation claim while still using the same active ingredient. Formulation patents therefore usually have narrower technical scope than a composition-of-matter patent.

Polymorph and solid-state patents

A polymorph patent can claim a particular crystalline form, XRPD pattern, DSC profile, water content, or solid-state composition of rasagiline mesylate. Such a patent may remain relevant after the original compound patent expires if the generic product uses the protected form.

The legal analysis depends on whether the claim is limited to:

• A pure polymorph;
• A composition containing the polymorph;
• A process for making the polymorph;
• A pharmaceutical formulation comprising the polymorph.

A manufacturer can sometimes design around a solid-state patent by using a different form, amorphous material, or process, but the resulting product must still satisfy regulatory quality and bioequivalence requirements.

How did Paragraph IV challenges affect rasagiline?

After expiry of the core composition patent and the relevant regulatory exclusivities, generic manufacturers could seek FDA approval through the ANDA pathway. Earlier entry efforts would have required certification against listed patents.

Paragraph IV framework

A Paragraph IV certification asserts that an Orange Book-listed patent is invalid, unenforceable, or will not be infringed by the proposed generic product. The reference-product sponsor may file a patent-infringement action within 45 days, triggering a statutory stay of ANDA approval for up to 30 months, subject to court action and statutory exceptions.

For rasagiline, the commercial importance of a Paragraph IV challenge depended on whether the challenged patent was:

• The core composition patent;
• A later method patent;
• A formulation or solid-state patent;
• Still listed and unexpired when the generic sought approval.

Once US 5,532,415 expired, a Paragraph IV challenge against that patent ceased to provide a meaningful route to earlier entry because the patent itself no longer blocked approval or launch.

Generic launch scenarios

Scenario	Principal legal issue	Commercial result
Generic uses rasagiline mesylate after core expiry	Core composition claim is expired	Entry generally available, subject to other rights
Generic uses a different salt	Avoids literal salt limitation	Must still satisfy FDA pharmaceutical and bioequivalence requirements
Generic omits a patented indication	Section viii strategy may apply	Depends on label and method claims
Generic uses a different polymorph	May avoid a polymorph claim	Requires control of identity, purity, dissolution, and stability
Generic changes excipients	May avoid formulation claims	Bioequivalence and product-quality requirements remain
Generic launches before all listed patents expire	Litigation and injunction risk	Timing depends on certifications, court rulings, and settlements

What litigation and settlements affected Azilect?

The key litigation risk for Azilect was associated with generic ANDA filings and challenges to listed patents. The existence of a Paragraph IV notice does not itself establish invalidity or infringement. The relevant issues typically included:

• Whether rasagiline mesylate was covered by the listed composition patent;
• Whether later patents claimed an approved use or formulation;
• Whether the generic label induced infringement;
• Whether the patent was valid over prior art;
• Whether a settlement permitted an agreed launch date.

The original composition patent was the strongest patent category because it did not depend on proving a particular use or formulation. After its expiration, later patents could delay only the products or uses within their specific claim scope.

A complete current litigation assessment requires the federal docket, FDA Orange Book records, and any settlement documents for each ANDA filer. The key business point is that no litigation involving an expired patent can restore the expired composition exclusivity.

How strong was the patent estate for rasagiline?

Historical strength

US 5,532,415 had high historical commercial value because it was:

• A composition-of-matter patent;
• Directed to the marketed active ingredient;
• Independent of a specific formulation;
• Independent of a particular dose or indication;
• Difficult to design around while retaining rasagiline mesylate as the active substance.

Its vulnerability would have focused on conventional composition-patent defenses:

• Anticipation;
• Obviousness;
• Written description;
• Enablement;
• Incorrect stereochemical characterization;
• Salt formation and inherent disclosure issues;
• Inventorship or priority defects;
• Patent-term limitations.

Current strength

Its current enforceability is zero because the patent has expired. Its remaining value is historical, evidentiary, and landscape-related. It may still help identify the originator’s compound, priority chain, inventors, and technical disclosure, but it cannot support an infringement action against current US sales.

Relative strength by patent type

Patent category	Historical blocking strength	Design-around difficulty	Current relevance
Rasagiline mesylate composition	Very high	High	Historical only
Method of treatment	Moderate to high	Moderate	Depends on claim and label
Tablet formulation	Moderate	Often moderate to high	Product-specific
Polymorph or solid-state form	Moderate	Moderate	Depends on form used
Manufacturing process	Low to moderate	Often higher	Relevant only to accused process
Packaging or stability	Low	Usually lower	Limited commercial scope

How does rasagiline mesylate compare with competing Parkinson’s drugs?

Rasagiline competes with other monoamine oxidase-B inhibitors and broader Parkinson’s therapies, including selegiline, safinamide, levodopa combinations, dopamine agonists, and catechol-O-methyltransferase inhibitors.

Product or ingredient	Mechanism or role	Core patent profile	Generic or biosimilar issue
Rasagiline mesylate	Selective MAO-B inhibitor	Original compound patent expired; later rights may be product-specific	Small-molecule generic competition
Selegiline	MAO-B inhibitor	Older compound and formulation rights	Generic competition established
Safinamide	MAO-B inhibitor with additional pharmacology	Later-generation composition and use patents	Patent and regulatory exclusivity depend on product
Levodopa/carbidopa	Dopamine replacement combination	Mature combination and delivery technologies	Generic and formulation competition
Rotigotine	Dopamine agonist	Transdermal delivery and formulation rights	Device and formulation issues may matter
Entacapone combinations	COMT inhibition with levodopa	Combination and formulation patents	Generic entry depends on product configuration

Rasagiline’s original estate was stronger than a formulation-only estate because the active compound claim covered the molecule in the marketed salt form. That advantage disappeared after expiration.

What manufacturing and IP barriers remain?

After expiry of US 5,532,415, the main barriers are regulatory and technical rather than compound-patent barriers.

Manufacturing barriers

A rasagiline manufacturer must control:

• Enantiomeric purity;
• Residual propargyl-related impurities;
• Salt formation;
• Particle-size distribution;
• Polymorphic or amorphous content;
• Degradation products;
• Stability under storage;
• Batch-to-batch assay and dissolution;
• API and finished-dose manufacturing compliance.

These controls can make development costly without creating patent exclusivity.

IP barriers

Remaining IP exposure may involve:

• A particular crystalline form;
• A pharmaceutical composition;
• A controlled-release product;
• A dose regimen;
• A combination treatment;
• A manufacturing process;
• A formulation with defined stability or dissolution characteristics.

Freedom-to-operate analysis should test the actual API form, formulation, manufacturing route, proposed label, and target jurisdictions. A patent that is irrelevant to a standard immediate-release tablet may still affect an extended-release product or a method-specific label.

What is the geographic coverage of US Patent 5,532,415?

US 5,532,415 provided rights only in the United States. Parallel patent rights would have been required in Europe, Canada, Japan, Israel, and other markets.

The US expiration did not automatically determine foreign status. Patent terms, patent-term extensions, supplementary protection certificates, opposition outcomes, and national-phase prosecution could differ by country.

Jurisdiction	Effect of US 5,532,415
United States	US rights only; patent expired
European Union	Requires separate national or regional patent analysis
Canada	Requires Canadian patent and regulatory review
Japan	Requires Japanese patent and regulatory review
Israel	Requires Israeli patent and regulatory review
Other markets	No direct legal effect from the US patent

Key Takeaways

• US Patent 5,532,415 is the foundational rasagiline mesylate composition patent.
• Its sole claim covers the R(+) enantiomer of N-propargyl-1-aminoindan as the mesylate salt.
• It does not expressly claim a tablet, dosage regimen, Parkinson’s indication, formulation, or manufacturing process.
• The claim was historically difficult to design around while using rasagiline mesylate as the active ingredient.
• The patent expired and no longer blocks US generic marketing.
• Current risk analysis must focus on later formulation, polymorph, method-of-use, and process patents.
• A Paragraph IV challenge to the expired composition patent no longer creates meaningful current entry risk.
• FDA approval, Orange Book listings, patent term, and patent enforceability are separate legal concepts.
• US status cannot be used to infer the status of parallel foreign rights.
• Rasagiline is a small-molecule generic opportunity, not a biosimilar opportunity.

FAQs

Is US Patent 5,532,415 a patent on Azilect itself?

Yes. It is the core composition patent covering rasagiline mesylate, the active ingredient in Azilect.

Does the patent cover rasagiline free base?

The claim expressly covers the mesylate salt. It does not expressly recite rasagiline free base.

Can a generic company sell rasagiline mesylate after the patent expired?

Yes, subject to FDA approval and any separate, unexpired patents covering the proposed formulation, method of use, solid-state form, or manufacturing process.

Does a different rasagiline polymorph avoid US Patent 5,532,415?

Not necessarily. The original claim is directed to the mesylate salt rather than expressly to a named crystal form. A different polymorph could still be rasagiline mesylate, while separate polymorph patents may create additional risk.

Are biosimilar rules relevant to rasagiline?

No. Rasagiline is a chemically synthesized small molecule. FDA approval of a competing product generally proceeds through the ANDA pathway rather than the biosimilar pathway.

References

1. U.S. Patent and Trademark Office. (1996). U.S. Patent No. 5,532,415: Mesylate salt of R(+)-N-propargyl-1-aminoindan.
2. U.S. Food and Drug Administration. (2006). Azilect (rasagiline mesylate) prescribing information.
3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
4. U.S. Food and Drug Administration. (n.d.). Hatch-Waxman amendments and abbreviated new drug applications.
5. U.S. Code, 35 U.S.C. §§ 154, 156, 271, 355.

Drugs Protected by US Patent 5,532,415

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: 5,532,415

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

International Family Members for US Patent 5,532,415

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