Details for Patent: 11,033,521

Which drugs does patent 11,033,521 protect, and when does it expire?

Patent 11,033,521 protects DHIVY and is included in one NDA.

This patent has seven patent family members in six countries.

Summary for Patent: 11,033,521

Title:	Levodopa fractionated dose composition and use
Abstract:	There is provided a convenient new treatment of Parkinson disease by a frequent administration of optimal levodopa doses mimicking a continuous intravenous or infusion treatment, thus mitigating motor complications; and a new carbidopa/levodopa pharmaceutical unit form providing said new treatment.
Inventor(s):	Thomas N CHASE, Kathleen E. Clarence-Smith
Assignee:	AVION PHARMACEUTICALS LLC
Application Number:	US16/719,203
Patent Claim Types: see list of patent claims	Use; Composition; Formulation; Dosage form;

United States Patent 11,033,521: Scope, Claim Construction, Exclusivity and Patent Landscape for Carbidopa/Levodopa Multiscore Tablets

U.S. Patent No. 11,033,521 protects a specific carbidopa/levodopa dosing system built around a quarterable bilayer tablet. Its strongest protection is the combination of a 25 mg/100 mg immediate-release tablet, four equal 6.25 mg/25 mg sections, an inert bottom layer, and dosing intended to approximate continuous levodopa exposure. The patent does not broadly protect carbidopa/levodopa, levodopa treatment, or continuous dopaminergic therapy in the abstract.

The patent creates two principal enforcement positions:

1. A composition-of-matter-style product claim directed to the physical tablet architecture.
2. Method claims directed to administering the quarter-tablet or half-tablet doses, generally up to nine times daily, for Parkinson's disease, motor fluctuations, levodopa-responsive disorders, hypersensitivity, dystonia, or pediatric treatment.

The tablet limitations make direct infringement comparatively identifiable. The treatment claims are broader in patient population and dosing purpose but depend on proof of the prescribed dose, tablet structure, and intended pharmacokinetic effect.

What does U.S. Patent 11,033,521 protect?

The patent protects a multiscore bilayer carbidopa/levodopa tablet and methods of using it to deliver small, repeated immediate-release doses.

Claim group	Claims	Principal subject matter
Treatment method	1-9	Parkinson's disease or levodopa-responsive disorders; 6.25/25 mg or 12.5/50 mg dosing; up to nine administrations daily
Tablet product	10-11	25 mg/100 mg bilayer tablet divided into four 6.25 mg/25 mg sections
Hypersensitivity and special populations	12-16	Hypersensitive patients, minors, generalized dystonia, twice- or three-times-daily dosing
Motor complications	17-20	Treatment or alleviation of Parkinsonian motor response complications

The patent's central technical concept is not a new active ingredient. It is dose subdivision through a scored tablet that allows one 25 mg/100 mg tablet to be administered as:

• One quarter: 6.25 mg carbidopa/25 mg levodopa.
• One half: 12.5 mg carbidopa/50 mg levodopa.
• Three quarters: 18.75 mg carbidopa/75 mg levodopa, although that dose is not expressly listed as an effective dose in the independent method claims.
• Whole tablet: 25 mg carbidopa/100 mg levodopa.

The claims require a top layer containing the active ingredients and an inert bottom layer containing no active ingredients. The scores must partially penetrate the bottom layer. That requirement distinguishes the claimed tablet from an ordinary monolayer scored tablet.

What are the key limitations in independent claims 1, 10, 12 and 17?

Claim 1: repeated low-dose treatment

Claim 1 requires all of the following:

• Treatment of Parkinson's disease or an LD-responsive disorder.
• Oral administration.
• Carbidopa/levodopa at either 6.25/25 mg or 12.5/50 mg.
• Administration intended to simulate continuous intravenous levodopa.
• Administration up to nine times per day.
• The drug must be present in a 25 mg/100 mg tablet.
• The tablet must have a fully scored top active layer.
• Three scores must create four sections.
• The scores must partially penetrate an inert bottom layer.
• Each section must contain 6.25 mg carbidopa and 25 mg levodopa.

A product using the same dose but a conventional single-layer tablet would not satisfy the tablet limitations of claim 1. Conversely, a structurally compliant tablet used once daily would not satisfy the claimed repeated-dose regimen.

Claim 10: the core product claim

Claim 10 is the most commercially important claim because it is directed to the tablet itself rather than a particular patient or clinical use.

The claim requires:

• Carbidopa: 25 mg total.
• Levodopa: 100 mg total.
• Immediate-release formulation.
• Fully scored top layer.
• Three scores producing four sections.
• Inert bottom layer without active ingredients.
• Scores that partially penetrate the inert layer.
• 6.25 mg carbidopa and 25 mg levodopa in each section.

Claim 10 does not require a Parkinson's indication, a particular dosing frequency, or a continuous plasma concentration. It may therefore provide the clearest basis for product-focused enforcement against a structurally equivalent generic.

Claim 12: hypersensitivity and special populations

Claim 12 repeats the core tablet and low-dose limitations but narrows the patient to one who is hypersensitive to levodopa. Claims 13-16 cover:

• Minor children.
• Generalized dystonia.
• Twice-daily or three-times-daily use.
• 12.5 mg/50 mg administered twice daily.

These claims may have narrower commercial significance because the patient-status limitations can complicate infringement proof. They may still have value where a product label expressly identifies pediatric, dystonia, or levodopa-sensitivity use.

Claim 17: motor response complications

Claim 17 targets patients with motor response complications related to Parkinson's disease or another LD-responsive disorder. Claims 18-20 focus on five-to-nine administrations per day and the asserted achievement of stable levodopa exposure without motor response complications.

These claims are clinically aligned with wearing-off and other levodopa-response problems. They are more dependent than claim 10 on clinical records, prescribing instructions, and evidence of the intended treatment outcome.

How does the patent's tablet technology work?

The claimed tablet uses a bilayer construction:

Layer	Required content	Function
Top layer	Carbidopa, levodopa and pharmaceutical carrier	Immediate-release active layer
Bottom layer	Pharmaceutical carrier without active ingredients	Inert support layer
Scores	Three scores through the active layer and partly into the bottom layer	Divide the top layer into four dose sections

The partial penetration limitation is important. It appears designed to permit separation of the active top layer into accurate quarter doses while retaining an integrated support layer. A competing tablet may avoid claim 10 if its scores do not penetrate the inert layer, if the active layer is not fully scored, or if the formulation is monolithic rather than bilayered.

Claim 11 adds an orally disintegrable formulation. That limitation may be relevant to rapidly disintegrating or orally disintegrating tablets, but it does not apply to every formulation covered by claim 10.

When does U.S. Patent 11,033,521 expire?

The patent issued on June 15, 2021. Its expiration date cannot be established from the claims alone because U.S. patent term depends on the earliest effective nonprovisional filing date, continuation history, terminal disclaimers, patent-term adjustment, and any patent-term extension. The controlling records are the patent face page, USPTO Patent Center, and any terminal-disclaimer documents.

The practical exclusivity endpoint should therefore be taken from the current USPTO record rather than calculated as 20 years from the issue date. The patent does not receive a new 20-year term beginning in 2021.

FDA regulatory exclusivity is separate. A patent listing in the Orange Book does not itself establish FDA exclusivity, and FDA approval of a generic does not automatically resolve patent infringement.

What is the Orange Book status of the patent?

The Orange Book relevance of U.S. Patent 11,033,521 depends on whether the patent is listed against an approved carbidopa/levodopa product and whether the listing covers the approved product's formulation or method of use.

The relevant regulatory questions are:

• Whether the patent is listed for an approved 25 mg/100 mg immediate-release product.
• Whether the listed claims cover the dosage form, method of use, or both.
• Whether the listing has been challenged under an ANDA paragraph IV certification.
• Whether the patent is listed as an active ingredient, formulation, or method-of-use patent.
• Whether any use code limits the scope of a section viii carve-out.

A formulation patent of this type generally has greater Orange Book relevance than a treatment claim that does not correspond to an approved labeling indication. A method-of-use listing may be susceptible to a section viii statement if the generic label omits the patented use, although the tablet-structure limitations in claim 10 would not ordinarily be avoided through a use carve-out.

FDA's Orange Book identifies patents and exclusivity associated with approved drug products. It does not determine claim validity or infringement. [1]

What generic entry risks exist for carbidopa/levodopa products?

Generic entry risk differs sharply by product design.

Generic design	Risk under claim 10	Principal issue
Conventional monolayer 25/100 tablet	Lower	No inert bilayer or partial score penetration
Bilayer 25/100 tablet with four active sections	High	Likely reads on the core product claim
Bilayer tablet with scores stopping at the top-layer/bottom-layer interface	Moderate	Potential noninfringement based on score penetration
Whole-tablet 25/100 product without quarter-dose sections	Lower	May lack four claimed sections
Orally disintegrating bilayer tablet	High if structurally compliant	Claim 11 may apply
6.25/25 mg tablet manufactured as a separate unit	Unclear to lower under claim 10	May avoid the claimed 25/100 tablet architecture
Extended-release product	Lower under the immediate-release limitation	Different release profile and formulation

A generic manufacturer seeking approval for the same multiscore bilayer design would face a higher risk of a paragraph IV challenge than a manufacturer offering a standard carbidopa/levodopa tablet. The most defensible design-around strategies would focus on:

• Removing the inert bottom layer.
• Using a monolayer tablet.
• Changing the scoring geometry.
• Avoiding score penetration into the bottom layer.
• Marketing separate 6.25/25 mg or 12.5/50 mg units.
• Using a different total strength or release profile.

The separate-unit strategy could create manufacturing and regulatory burdens because it may require a new strength, new tablet dimensions, new bioequivalence work, and a different dosage regimen.

How strong is the patent estate?

The estate is strongest against a direct copy of the claimed tablet. Claim 10 has a relatively concrete structural profile that can be assessed through inspection, cross-section analysis, assay of separated sections, and manufacturing records.

The method claims are more vulnerable to claim-construction and proof disputes.

Strengths

• Claim 10 is product-focused and does not depend on a specific diagnosis.
• The four-section architecture is technically specific.
• The inert bottom layer and partial score penetration provide identifiable structural limitations.
• The 6.25/25 mg quarter-dose composition is commercially meaningful.
• Claims 1, 17 and 20 connect the tablet to frequent dosing and motor fluctuation management.

Vulnerabilities

• Carbidopa/levodopa 25/100 mg tablets and frequent levodopa dosing were established technologies before the patent.
• The inventive-step case may depend on whether the particular bilayer scoring design would have been obvious from known scored tablets and Parkinson's dosing practices.
• "Simulate continuous intravenous administration" may be disputed as a functional or intended-use limitation.
• "Full efficacy" and "no motor response complications" may raise definiteness, written-description, or enablement issues.
• "Fully scored" and "partially penetrates" require technical construction and testing.
• The claimed outcomes may be difficult to prove consistently across patients.

The patent is therefore more defensible as a formulation and device-style patent than as a broad clinical-treatment patent.

What prior-art and validity issues are most relevant?

The principal prior-art categories are:

1. Immediate-release carbidopa/levodopa tablets.
2. Standard 25 mg/100 mg Sinemet-type dosage forms.
3. Scored or multiscore tablets.
4. Bilayer tablets with inert support layers.
5. Quarter-dose administration.
6. Frequent levodopa dosing for wearing-off.
7. Continuous levodopa infusion and pharmacokinetic smoothing.
8. Orally disintegrating carbidopa/levodopa formulations.
9. Pediatric and dystonia treatment using low-dose levodopa.

A validity challenge would likely combine references rather than rely on a single document. The product claim's defense would focus on the specific interaction between the bilayer structure, score penetration, section uniformity and immediate release. The method claims would face a stronger obviousness argument if the prior art taught low-dose, frequent administration and the tablet structure was viewed as a predictable delivery solution.

The record should be reviewed for terminal disclaimers, continuation applications, cited references, and prosecution amendments. Narrow prosecution amendments can materially limit the scope of "fully scored," "bilayered," "inert," and "partial penetration."

Which companies are challenging the patent?

No challenger, ANDA applicant, paragraph IV notice, district-court complaint, or settlement agreement can be attributed solely from the claim text provided. A definitive competitor and litigation assessment requires matching the patent against current USPTO, FDA Orange Book, PACER, and Abbreviated New Drug Application records.

Potential commercial exposure is highest for a manufacturer seeking to copy a branded or authorized-generic product that uses the same four-section bilayer tablet. Conventional carbidopa/levodopa generic manufacturers face materially lower risk if their products use ordinary monolayer tablets.

What patent litigation affects the product?

The likely litigation issues are:

• Whether a proposed tablet has an inert bottom layer.
• Whether the scores partially penetrate that layer.
• Whether each quarter contains the required active amounts.
• Whether the product is immediate release.
• Whether a generic label induces use five to nine times daily.
• Whether a section viii carve-out can remove the patented motor-complication or continuous-exposure use.
• Whether the claimed clinical results are limiting or merely intended use.

Laboratory testing would be central to a claim 10 case. Labeling, prescribing data, formulation records and clinical protocols would matter more for claims 1-9 and 17-20.

How does this patent compare with competing carbidopa/levodopa patent strategies?

Patent strategy	Typical protection	Relative strength
Active ingredient patent	New chemical entity	Not applicable to conventional carbidopa/levodopa
Extended-release formulation patent	Controlled plasma exposure	Often broad commercial relevance
Infusion or pump patent	Continuous levodopa delivery	Different route and device profile
Method-of-use patent	Wearing-off, dyskinesia, or dosing regimen	Dependent on label and clinical use
U.S. 11,033,521	Bilayer, four-section, immediate-release tablet	Strongest against structural copies

The patent occupies a formulation niche between conventional tablets and continuous-infusion systems. It attempts to obtain smoother levodopa exposure through repeated oral microdosing rather than through a new active ingredient or an infusion device.

Key Takeaways

• U.S. Patent 11,033,521 primarily protects a 25 mg/100 mg, four-section, bilayer carbidopa/levodopa tablet.
• Claim 10 is the principal product claim and the clearest enforcement anchor.
• The required inert bottom layer and partial score penetration are important design limitations.
• The method claims cover low-dose, frequent oral administration intended to approximate continuous levodopa exposure.
• Generic risk is highest for a structurally identical bilayer tablet and lower for conventional monolayer products.
• The claims may face obviousness challenges based on known carbidopa/levodopa dosing, scored tablets, bilayer technology and continuous-exposure treatment concepts.
• The patent's expiration date must be confirmed from USPTO term records because issue date alone does not establish the statutory endpoint.
• Orange Book listing, paragraph IV challenges, litigation and settlements cannot be reliably assigned from the claim language alone.

Frequently Asked Questions

Does U.S. Patent 11,033,521 cover all carbidopa/levodopa 25/100 mg tablets?

No. The claims require a specific multiscore bilayer structure, including four active sections and an inert bottom layer. A conventional monolayer 25/100 mg tablet generally would not satisfy those structural limitations.

Can a generic avoid the patent by selling separate 6.25 mg/25 mg tablets?

Potentially, because claim 10 requires the four doses to be present in one 25 mg/100 mg multiscore tablet. Separate-unit products would still require independent analysis of the method claims and any other patents.

Does an orally disintegrating tablet infringe the patent?

It may. Claim 11 expressly covers an orally disintegrable formulation, but the tablet must first satisfy all limitations of claim 10, including the bilayer and score-penetration requirements.

Is continuous intravenous administration required in actual treatment?

No. The claims require oral administration at a regimen intended to simulate continuous intravenous levodopa administration. They do not require the patient to receive intravenous levodopa.

Can a generic omit the patented use from its label?

A use carve-out may reduce risk for method-of-use claims if the omitted use is legally separable. It would not ordinarily avoid a product claim directed to the physical tablet itself.

References

1. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/orange-book
2. U.S. Patent and Trademark Office. (2024). Patent Center. https://patentcenter.uspto.gov/
3. U.S. Patent No. 11,033,521. (2021). Multiscore bilayered carbidopa/levodopa tablet and methods of use. U.S. Patent and Trademark Office.
4. U.S. Food and Drug Administration. (2021). Dhivy: Carbidopa and levodopa tablets, prescribing information. FDA-approved labeling.

Drugs Protected by US Patent 11,033,521

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Avion Pharms	DHIVY	carbidopa; levodopa	TABLET;ORAL	214869-001	Nov 12, 2021		RX	Yes	Yes	11,033,521		Y			TREATMENT OF PARKINSON'S DISEASE
Avion Pharms	DHIVY	carbidopa; levodopa	TABLET;ORAL	214869-001	Nov 12, 2021		RX	Yes	Yes	11,033,521		Y			METHOD OF TREATING PARKINSON'S DISEASE BY ORALLY ADMINISTERING SEGMENTS OF A FUNCTIONALLY MULTISCORED, BILAYERED TABLET HAVING CARBIDOPA—25 MG/LEVODOPA—100 MG, EACH SEGMENT HAVING CARBIDOPA—6.25 MG/LEVODOPA—25 MG
Avion Pharms	DHIVY	carbidopa; levodopa	TABLET;ORAL	214869-001	Nov 12, 2021		RX	Yes	Yes	11,033,521		Y			METHOD OF TREATING PARKINSON'S DISEASE BY ORALLY ADMINISTERING A FUNCTIONALLY MULTISCORED, BILAYERED TABLET HAVING CARBIDOPA—25 MG/LEVODOPA—100 MG

International Family Members for US Patent 11,033,521

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Brazil	112020017422
Canada	3095341
China	111954523
European Patent Office	3773532
Japan	2021517128
Japan	2022133449
World Intellectual Property Organization (WIPO)	2019191353