US Patent 7,815,942: Rasagiline Particle-Size, Formulation, and Manufacturing Claims

US Patent 7,815,942 protects pharmaceutical compositions containing particle-size-controlled rasagiline salt, particularly rasagiline mesylate. Its principal commercial target is oral rasagiline tablets used in Parkinson's disease. The patent does not claim rasagiline as a molecule. It claims particle-size distributions, blend and content uniformity, solid dosage forms, treatment methods, and manufacturing controls built around those particle characteristics.

The strongest claim cluster is directed to rasagiline salt particles in which more than 90% by volume measure between greater than 6 microns and less than 250 microns, with narrower dependent ranges below 220 and 200 microns. The patent also claims granulation, tablet manufacture, blend-uniformity testing, and finished-dosage-form uniformity.

The relevant active ingredient is R(+)-N-propargyl-1-aminoindan, commonly known as rasagiline. The most commercially relevant salt is rasagiline mesylate, the active pharmaceutical ingredient in Azilect and generic rasagiline tablets.[1][2]

What does US Patent 7,815,942 protect?

The patent protects a physical and manufacturing profile for rasagiline salt rather than a new pharmacological entity.

Protection category	Representative claims	Practical scope
Particle-size-controlled rasagiline salt	1-5	Rasagiline salt particles with more than 90% by volume above 6 microns and below 250, 220, or 200 microns
Specific salts	4-5	Tartrate, esylate, mesylate, and sulfate; mesylate receives the narrowest dependent protection
Solid compositions	6-15, 26-33	Rasagiline particles combined with a carrier, including granulates and tablets
Uniformity limitations	12-15	RSD below 4%, 3%, or 2%; content uniformity from 95% to 105%
Parkinson's treatment method	16, 34-35	Administration of a qualifying solid composition
Particle-size-reduction process	17-19	Comminution or other reduction into the claimed range
Granulation and compression	20-24, 36-37	Blending, granulation, compression, and tablet formation
In-process quality control	21-22, 25	Testing blend uniformity before forming the final composition

The patent's central technical proposition is that particle size affects the ability to manufacture a low-dose solid dosage form with acceptable blend and content uniformity. Rasagiline is administered at relatively low doses, which makes segregation, sampling error, and nonuniform distribution important manufacturing issues.

How do the particle-size claims operate?

Claim 1 is the principal composition claim. It requires:

A mixture of particles.
A pharmaceutically acceptable salt of R(+)-N-propargyl-1-aminoindan.
More than 90% of the total particle amount by volume above 6 microns.
More than 90% below 250 microns.

The claim is a distribution claim, not a requirement that every particle fall within the range. A batch may contain particles outside the stated limits, provided the more-than-90%-by-volume condition is satisfied.

Claims 2 and 3 narrow the upper limit:

Claim 2: below 220 microns.
Claim 3: below 200 microns.

Claims 4 and 5 narrow the salt identity. Claim 5 is commercially important because it limits the salt to rasagiline mesylate.

What is the significance of the 6-micron lower limit?

The lower limit excludes excessive fines. Very small particles can increase electrostatic effects, cohesion, dust generation, and segregation during blending. A particle population with a large fraction below 6 microns may fall outside claim 1 even if its upper particle-size limit is compliant.

What is the significance of the 250-micron upper limit?

The upper limit controls oversized particles that may produce poor dissolution, nonuniform feeding, or segregation in a low-dose blend. A product with more than 10% of its volume at or above 250 microns may avoid claim 1, depending on the applicable particle-size measurement method and the evidence used to establish the distribution.

Particle-size measurement methodology is likely to be central in any infringement dispute. Laser diffraction, sieve analysis, sampling location, wet versus dry dispersion, agglomerate treatment, and volume-weighting assumptions can materially affect the result.

Which claims are strongest commercially?

The composition claims and process claims present different enforcement advantages.

Composition claims 1-15

Composition claims can reach an accused product after manufacture and distribution. Claims 1, 2, and 3 establish the particle-size core. Claims 6-15 add carriers, granulation, dosage-form status, and uniformity parameters.

Claims 11-15 are narrower because they require an oral tablet and quantitative uniformity characteristics. They may be easier to design around but may provide stronger technical evidence when a marketed tablet matches the claimed profile.

Method claim 16

Claim 16 covers treatment of Parkinson's disease using a qualifying solid composition. Method claims can be relevant where the product label instructs use for Parkinson's disease. Their enforcement may depend on the approved labeling and the relationship between the claimed formulation and the labeled indication.

The claim is narrower than a composition claim because it requires administration to a Parkinson's patient. It is less useful against a manufacturer that does not directly perform the treatment step, although induced-infringement theories may arise from labeling and promotional conduct.

Process claims 17-25

The process claims cover:

Comminution of rasagiline salt.
Particle-size reduction into the claimed range.
Blending with a carrier.
Granulation.
Blend-uniformity testing.
Compression into tablets.
Forming the composition only when predetermined blend criteria are met.

These claims are potentially significant because the manufacturing process is usually not visible from the finished product. Enforcement may require discovery of batch records, equipment settings, validated particle-size methods, in-process test results, and manufacturing-site documents.

Claim 25 is particularly process-specific. It requires a sequence in which a batch is comminuted, admixed, tested for blend uniformity, and used to prepare the composition only if predetermined criteria are met.

How broad is the salt coverage?

Claim 4 identifies four salt classes:

Salt identified in the patent	Coverage
Tartrate	Expressly claimed
Esylate	Expressly claimed
Mesylate	Expressly claimed and separately narrowed in claim 5
Sulfate	Expressly claimed

Rasagiline mesylate is the commercially relevant embodiment. A different pharmaceutically acceptable rasagiline salt may avoid claims limited by claim 4, but it would still need to be assessed against claim 1 if claim 1 is interpreted to cover the salt generically.

The patent does not claim the free base in the provided claim set. A product using rasagiline free base would face a different analysis involving claim construction, salt conversion during manufacturing, and whether the marketed composition contains the claimed salt.

What formulations are protected by US 7,815,942?

The patent covers solid formulations that contain the qualifying particle mixture and a carrier. The claim set expressly reaches:

Granulates.
Solid dosage forms.
Oral dosage forms.
Tablets.
Dosage forms with RSD below 4%, 3%, or 2%.
Dosage forms with content uniformity from 95% to 105%.

The patent does not expressly require a particular excipient. A carrier may include conventional pharmaceutical diluents, binders, disintegrants, lubricants, glidants, or other excipients, provided the accused formulation satisfies the claim limitations.

The formulation claims do not require a specific release profile. The provided claims therefore appear directed to immediate-release or conventional oral solid products unless another claim or specification limitation imposes a release requirement.

How do the uniformity claims affect infringement risk?

Claims 12-15 introduce finished-dosage-form performance limitations:

RSD less than 4%.
RSD less than 3%.
RSD less than 2%.
Content uniformity between 95% and 105%.

These limitations may create a significant evidentiary issue. A manufacturer could have a qualifying particle-size distribution but fail to meet the claimed RSD or content-uniformity threshold. Conversely, a tablet can meet a uniformity threshold without necessarily satisfying the claimed particle-size distribution.

The claims require careful separation of:

Blend uniformity.
Dosage-form content uniformity.
Relative standard deviation.
The population tested.
The analytical method and acceptance criteria.

Claims 21 and 22 address blend uniformity, while claims 12-15 address solid dosage forms. Test results for the granulate do not automatically establish compliance with the dosage-form claims.

What is the FDA regulatory status of rasagiline?

Rasagiline mesylate was approved by the FDA as Azilect under NDA 021641. The approved product is an oral tablet used for Parkinson's disease, both as monotherapy and as adjunctive therapy with levodopa in the approved labeling.[2]

FDA milestone	Status
Active ingredient	Rasagiline mesylate
Reference product	Azilect
Reference applicant	Teva Pharmaceuticals
Dosage form	Oral tablet
Regulatory pathway for generics	ANDA
FDA exclusivity type	Original new chemical entity exclusivity applied at initial approval
Biosimilar pathway	Not applicable

Rasagiline is a small-molecule drug. Biosimilar approval under section 351(k) of the Public Health Service Act is not relevant. Generic applicants use the ANDA pathway and must demonstrate pharmaceutical equivalence and bioequivalence to the reference listed drug.[3]

What is the Orange Book status of US Patent 7,815,942?

The Orange Book is the relevant source for determining whether the patent was listed against the reference product and whether an ANDA applicant had to make a Paragraph IV certification.[1]

US Patent 7,815,942 was associated with the rasagiline tablet patent estate and was relevant to generic challenges. Its commercial significance derived from the fact that it covered formulation and manufacturing attributes not captured by the earlier rasagiline compound and use patents.

The exact current listing status, delisting history, expiration date, and applicability to each strength must be determined from the FDA Orange Book patent listing for NDA 021641 and the applicable annual edition. Patent listing status can differ from underlying enforceability. A patent may remain listed while being subject to expiration, terminal disclaimer, invalidity findings, settlement restrictions, or a permitted generic launch.

When does US Patent 7,815,942 lose exclusivity?

The patent term is governed by the filing date, applicable patent-term adjustment, patent-term extension, and any terminal disclaimer. The issue date alone does not establish expiration.

The patent was issued on October 19, 2010. Its effective expiration must be calculated from the USPTO patent-term record rather than from the issue date.[4] The principal commercial question is whether the patent provided an enforceable barrier at the time generic rasagiline applicants filed Paragraph IV certifications and whether those applicants received an authorized launch date through settlement or licensing.

FDA drug exclusivity and patent exclusivity are separate:

Exclusivity type	Relevance to rasagiline
NCE exclusivity	Applied to the original Azilect approval and blocked ANDA submission for the statutory period
Patent exclusivity	Depends on the individual patent term and enforcement history
Pediatric exclusivity	Requires a qualifying FDA pediatric-extension award
Orphan exclusivity	Not the principal exclusivity basis for rasagiline
Biosimilar reference-product exclusivity	Not applicable

Which companies challenged the rasagiline patent estate?

Generic competition involved ANDA applicants seeking approval for rasagiline tablets, including companies that challenged Teva's listed patents through Paragraph IV certifications. The relevant litigation record must be reviewed by defendant, patent, dosage strength, and settlement date because different applicants may have reached different outcomes.

A Paragraph IV certification alleges that a listed patent is invalid, unenforceable, or not infringed. Under the Hatch-Waxman Act, an infringement action filed within 45 days can trigger a 30-month FDA approval stay, subject to statutory exceptions.[3]

The litigation issues most relevant to US 7,815,942 would include:

Whether the particle-size range was novel.
Whether the claimed distribution was obvious in view of milling and formulation prior art.
Whether the specification enabled the full claimed range.
Whether the claims were adequately supported by the disclosure.
Whether the accused generic product met the more-than-90%-by-volume limitation.
Whether the method claims were induced by the proposed label.
Whether the patent was subject to a terminal disclaimer or other term limitation.

What generic entry risks exist?

Generic entry risk should be analyzed across three scenarios.

Authorized entry before patent expiration

A settlement or license may permit an ANDA applicant to launch before the patent's nominal expiration. In that situation, the patent remains legally relevant but no longer functions as a complete market barrier against the licensed entrant.

Entry after patent expiration

Once the patent expires, the particle-size, formulation, and process claims no longer block ordinary commercial manufacture, subject to any separate unexpired patents.

Design-around entry

A generic manufacturer may seek to avoid infringement by using:

A different particle-size distribution.
A particle population with 10% or more outside the claimed volume range.
A different rasagiline salt.
A manufacturing process that does not use the claimed comminution or testing sequence.
A formulation that does not satisfy the claimed RSD or content-uniformity limitation.

Design-around effectiveness depends on the full patent family, claim construction, prosecution history, and any continuation or divisional patents. Avoiding claim 1 does not automatically avoid process claims 17-25.

How strong is the patent estate?

The patent is strongest where the innovator can establish all of the following:

The product contains rasagiline mesylate.
More than 90% by volume of particles are above 6 microns and below the applicable upper limit.
The product is a solid oral formulation.
The manufacturing records show comminution, granulation, or the claimed quality-control sequence.
The product meets the asserted uniformity limitations.

Its principal weakness is that particle-size and blend-uniformity claims are highly measurement-dependent. A well-designed generic development program can target a different particle distribution or use a documented process that avoids the sequencing and testing limitations.

The patent is also narrower than a compound patent. It cannot prevent all rasagiline products. It addresses products and manufacturing methods that fall within defined physical and process parameters.

What licensing and settlement issues affect commercial exposure?

Patent settlements in the rasagiline market can change the practical date of generic entry without changing the patent's statutory expiration. Key documents include:

ANDA litigation complaints.
Stipulated judgments.
Settlement agreements.
License agreements.
FDA approval letters.
Orange Book delisting or expiration records.

A settlement may include an authorized generic arrangement, supply terms, launch rights, or restrictions that differ by applicant. Revenue exposure therefore depends on the earliest authorized entrant, the number of licensees, and the extent to which the settlement permits multiple generic suppliers.

Key Takeaways

US Patent 7,815,942 is a formulation and manufacturing patent for particle-size-controlled rasagiline salt, not a basic rasagiline compound patent.
Claim 1 requires more than 90% by volume of particles to be above 6 microns and below 250 microns.
Claims 2 and 3 narrow the upper particle-size limit to 220 and 200 microns.
Rasagiline mesylate is the principal commercial embodiment and is separately claimed.
The patent reaches granulates, oral tablets, blend-uniformity controls, content uniformity, particle-size reduction, and compression processes.
Process claims may require manufacturing-record discovery because the claimed operations are not necessarily observable in the finished product.
Rasagiline is a small-molecule drug regulated through the ANDA pathway, not the biosimilar pathway.
Paragraph IV risk turns on particle-size testing, salt identity, formulation data, process evidence, obviousness, enablement, and patent-term calculations.
Generic launch may occur under settlement or license before the patent's nominal expiration.
The complete freedom-to-operate position requires review of the entire rasagiline patent family, Orange Book records, continuation patents, and litigation outcomes.

FAQs

Does US 7,815,942 cover all rasagiline tablets?

No. It covers rasagiline salt compositions and processes that satisfy the specific particle-size, formulation, uniformity, or manufacturing limitations in the asserted claims.

Can a generic avoid the patent by using rasagiline free base?

Possibly, but the answer depends on the final product, salt-conversion steps, manufacturing process, and other patents in the rasagiline estate. The provided claims expressly focus on pharmaceutically acceptable rasagiline salts.

Does particle size have to be measured by a specific method?

The claims provided do not identify a single measurement method. The specification, prosecution history, FDA filings, and accepted analytical method would control the infringement analysis.

Can a product infringe claim 1 but not claims 12 through 15?

Yes. A product may satisfy the particle-size distribution in claim 1 but fail the narrower tablet, RSD, or content-uniformity limitations in claims 12-15.

Are biosimilars a competitive threat to Azilect?

No. Rasagiline is a small molecule. Competition proceeds through generic ANDA filings rather than biosimilar applications.

References

U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations (Orange Book).
U.S. Food and Drug Administration. (2023). Azilect (rasagiline mesylate) prescribing information.
Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 355.
United States Patent and Trademark Office. (2010). U.S. Patent No. 7,815,942: Pharmaceutical compositions comprising R(+)-N-propargyl-1-aminoindan.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Teva	AZILECT	rasagiline mesylate	TABLET;ORAL	021641-001	May 16, 2006	AB	RX	Yes	No	7,815,942	⤷ Start Trial	Y	Y		TREATMENT OF PARKINSON'S DISEASE	⤷ Start Trial
Teva	AZILECT	rasagiline mesylate	TABLET;ORAL	021641-002	May 16, 2006	AB	RX	Yes	Yes	7,815,942	⤷ Start Trial	Y	Y		TREATMENT OF PARKINSON'S DISEASE	⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2006216696	⤷ Start Trial
Brazil	PI0608209	⤷ Start Trial
Canada	2600011	⤷ Start Trial
Canada	2901244	⤷ Start Trial
China	101123946	⤷ Start Trial
European Patent Office	1848402	⤷ Start Trial
Spain	2586412	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 7,815,942

Which drugs does patent 7,815,942 protect, and when does it expire?

Summary for Patent: 7,815,942