Details for Patent: 9,533,046

Which drugs does patent 9,533,046 protect, and when does it expire?

Patent 9,533,046 protects RYTARY and is included in one NDA.

This patent has twenty-five patent family members in twelve countries.

Summary for Patent: 9,533,046

Title:	Controlled release formulations of levodopa and uses thereof
Abstract:	The current invention provides a controlled release oral solid formulation of levodopa comprising levodopa, a decarboxylase inhibitor, and a carboxylic acid. Also provided by this invention is multiparticulate, controlled release oral solid formulations of levodopa comprising: i) a controlled release component comprising a mixture of levodopa, a decarboxylase inhibitor and a rate controlling excipient; ii) a carboxylic acid component; and iii) an immediate release component comprising a mixture of levodopa and a decarboxylase inhibitor.
Inventor(s):	Ann Hsu, Jim Kou, Laman Alani
Assignee:	Impax Laboratories LLC
Application Number:	US14/958,975
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,533,046
Patent Claim Types: see list of patent claims	Use; Composition; Formulation; Device; Dosage form;

# US Patent 9,533,046: Claim Scope, Rytary Patent Landscape, Generic Entry Risk, and Exclusivity

US Patent 9,533,046 protects a multiparticulate oral formulation and dosing method for Parkinson's disease that combines immediate-release carbidopa/levodopa with controlled-release beads, pellets, or granules. Its strongest protection is concentrated in three independent method claims: claim 1 requires a controlled-release carboxylic acid, claim 20 requires two controlled-release particle populations with different levodopa dissolution rates, and claim 23 narrows the acid requirement to tartaric acid.

The patent is associated with the Rytary carbidopa/levodopa extended-release product developed by Impax Laboratories, now within Amneal Pharmaceuticals. The patent was issued January 3, 2017, from a continuation application in a family directed to multiparticulate levodopa/carbidopa formulations. The statutory patent term is generally reported to expire May 29, 2029, before any applicable patent-term adjustment or disclaimer. [1]

What does US Patent 9,533,046 protect?

The patent protects a treatment method rather than a formulation in isolation. Literal infringement requires oral administration of a covered multiparticulate formulation to a human patient for Parkinson's disease or a specified related condition.

The patent has three independent claims:

Claim	Principal protected subject matter	Distinguishing limitation
1	Parkinson's treatment using immediate-release and controlled-release multiparticulates	Controlled release of carbidopa, levodopa, and a non-carbidopa/non-levodopa carboxylic acid, plus defined plasma profile
20	Parkinson's treatment using two controlled-release particle populations	First population has a slower in vitro levodopa dissolution profile than the second
23	Parkinson's treatment using immediate-release and controlled-release multiparticulates	Controlled-release component releases carbidopa, levodopa, and tartaric acid

All three independent claims require a formulation containing approximately 10 to 300 mg of carbidopa and 25 to 1,200 mg of levodopa. They also require an immediate-release component containing carbidopa and levodopa in a ratio of approximately 1:4.

The claims are therefore directed to a specific pharmacokinetic and multiparticulate delivery architecture, not to every extended-release carbidopa/levodopa product.

How broad are the independent claims?

Claim 1: acid-containing controlled-release formulation

Claim 1 has the broadest acid-related scope. The controlled-release component must contain more than one bead, pellet, or granule and must release:

• carbidopa;
• levodopa; and
• a carboxylic acid other than carbidopa or levodopa.

The acid-to-levodopa molar ratio must be greater than 1:4 and less than 4:1. Dependent claims narrow that ratio to progressively smaller windows, including:

• greater than 1:4 and less than 3:2;
• greater than 1:2 and less than 4:3; and
• greater than 2:3 and less than 5:4.

The claim lists tartaric, adipic, succinic, citric, benzoic, acetic, ascorbic, fumaric, lactic, malic, oleic, sorbic, stearic, palmitic, and other acids. Claim 12 specifically covers tartaric acid.

The acid may be in the same bead, pellet, or granule as carbidopa and levodopa, or in a different controlled-release particle population. Claims 13 and 14 create those alternative embodiments.

Claim 20: two-population dissolution architecture

Claim 20 omits the carboxylic-acid requirement. Its central limitation is the use of at least two different controlled-release populations:

1. a first population with a slower in vitro levodopa dissolution profile; and
2. a second population with a faster profile.

This claim can reach formulations that achieve the required pharmacokinetic profile without using tartaric acid or another organic acid, provided the product has the required particle populations and release characteristics.

Claim 21 adds a detailed dissolution test for the slower population. The first population must release:

Dissolution time	Maximum levodopa release
120 minutes	Less than 20%
150 minutes	Less than 40%
210 minutes	Less than 80%
260 minutes	100%

The test uses a USP basket apparatus at 75 rpm, simulated gastric fluid for the first 120 minutes, and simulated intestinal fluid thereafter. This limitation gives claim 21 greater technical specificity but also creates a measurable design-around target.

Claim 22 requires that the second population contain a carbidopa/levodopa core with an enteric coating.

Claim 23: tartaric-acid formulation

Claim 23 is narrower than claim 1 because it expressly requires tartaric acid. It does not require the two different dissolution populations found in claim 20. A product could therefore fall within claim 23 through a single controlled-release particle architecture, so long as it contains the required immediate-release and tartaric-acid-containing controlled-release components and meets the plasma-profile limitations.

What pharmacokinetic profile must an accused product meet?

The patent claims an unusual concentration-time profile in addition to formulation structure. Following a single dose:

• the first concentration must occur within one hour of administration;
• the second concentration must occur after the first and must be the maximum concentration;
• the first concentration must be at least approximately 50% of the second;
• the third concentration must occur after the second and at least four hours after the second for claims 1 and 23;
• the third concentration must occur approximately six hours after administration for claim 20;
• the second-to-third concentration ratio must be approximately 1.5 to 2.5;
• levodopa concentrations must decrease after the third concentration; and
• plasma levels must not fluctuate by more than 40% between 0.5 and six hours after dosing.

Claims 7 and 8 clarify that the concentrations may be mean or median plasma concentrations. Claims 3 through 6 specify alternative timing and concentration relationships.

These limitations are important because they make infringement dependent on clinical or pharmacokinetic testing. A generic manufacturer could have a formulation with similar dissolution behavior but avoid infringement if its clinical profile fails one required concentration relationship. Conversely, a formulation that differs in excipients could still present risk if it produces the claimed particle structure and plasma profile.

What formulations are protected by US 9,533,046?

The patent covers the following principal formulation configurations:

Configuration	Covered claims
Immediate-release carbidopa/levodopa plus acid-containing controlled-release particles	Claims 1-19, 23-31
Tartaric-acid-containing controlled-release particles	Claims 12, 23, 26, 28, 31
Two controlled-release populations with different levodopa dissolution rates	Claims 20-22, 25, 27, 30
Same controlled-release particle contains carbidopa, levodopa, and acid	Claim 13
Acid is in a different particle from carbidopa and levodopa	Claim 14
Capsule dosage form	Claims 17, 27, 28
Sprinkled onto food or liquids	Claims 29-31
Enteric-polymer coating	Claims 24-26
Three-times-daily administration	Claim 9
Six-hour dosing interval	Claim 10
Secondary Parkinsonism	Claim 2

The claims do not require a particular capsule size, brand name, manufacturing site, or commercial excipient. They do require the claimed dosage ranges, release configuration, and pharmacokinetic performance.

When does US Patent 9,533,046 lose exclusivity?

The reported statutory expiration date is May 29, 2029. [1] The date reflects the patent family’s earliest effective nonprovisional filing date and should be evaluated together with any patent-term adjustment, terminal disclaimer, reexamination certificate, or post-grant proceeding reflected in the USPTO file history.

The patent did not create new chemical entity exclusivity for levodopa or carbidopa. Both active ingredients have long regulatory histories. Any FDA exclusivity associated with the Rytary approval is separate from the patent term and does not extend the patent expiration date. Rytary was approved by FDA on January 8, 2015, under NDA 204630. [2]

Exclusivity timeline

Event	Date
Rytary FDA approval	January 8, 2015
US Patent 9,533,046 issued	January 3, 2017
Reported statutory patent expiration	May 29, 2029
Earliest ordinary post-expiration generic entry point	May 29, 2029, subject to regulatory and litigation outcomes

The relevant commercial exclusivity period is controlled by the full Rytary Orange Book estate, not by US 9,533,046 alone.

What is the Orange Book status of Rytary and US 9,533,046?

Rytary is an FDA-approved extended-release capsule containing carbidopa and levodopa. The Orange Book is the controlling FDA source for patents submitted by the NDA holder and accepted for listing against the reference product. [3]

The Rytary patent estate has included multiple formulation and method-of-use patents, including US 8,685,574 and US 9,533,046, along with later continuation patents. The practical question for an ANDA applicant is whether its proposed label and product design are covered by one or more listed patents, not whether it avoids a single patent.

Patent listing status can change through delisting, expiration, correction, litigation, or FDA administrative action. A current freedom-to-operate analysis must therefore compare the live Orange Book entry for NDA 204630 with the complete continuation family.

Which companies are challenging the Rytary patent estate?

Rytary has attracted generic development because it is a branded extended-release levodopa product with a differentiated multiparticulate design. ANDA applicants face two separate risks:

1. a patent certification risk under the Hatch-Waxman framework; and
2. a formulation-performance risk arising from the claimed pharmacokinetic profile.

A Paragraph IV certification against a listed Rytary patent can trigger a 45-day infringement action and a potential 30-month stay of ANDA approval under 21 U.S.C. § 355(j). [4] A generic applicant may instead file a Paragraph III certification agreeing to defer approval until patent expiration, or submit a section viii statement where the relevant method of use can be carved out.

Publicly relevant competitors include manufacturers developing generic carbidopa/levodopa extended-release capsules and companies pursuing next-generation extended-release levodopa products. The critical distinction is that an applicant may avoid US 9,533,046 while remaining exposed to other Rytary patents.

No biosimilar pathway applies. Carbidopa/levodopa is a small-molecule drug, so competitive products are submitted through an ANDA or, in some cases, a 505(b)(2) application rather than a biosimilar application under section 351(k).

What patent litigation affects US 9,533,046?

The key litigation risk is ANDA litigation against a proposed generic Rytary product. For this patent, the asserted issues would likely include:

• whether the proposed product contains an immediate-release component with the claimed carbidopa/levodopa ratio;
• whether its controlled-release particles qualify as beads, pellets, or granules;
• whether an acid is released from the controlled-release component;
• whether the acid-to-levodopa molar ratio falls within the claimed range;
• whether the product has two particle populations with different dissolution profiles;
• whether the clinical or modeled plasma profile satisfies the claimed relationships; and
• whether the proposed label induces the claimed Parkinson's treatment method.

The patent’s method-claim format can create an evidentiary issue. A formulation manufacturer may argue that its product does not infringe until a physician administers it for the claimed indication. The patent holder may respond that the ANDA, proposed labeling, product composition, and expected use establish a statutory basis for infringement under the Hatch-Waxman framework.

Potential validity defenses include anticipation, obviousness, lack of written description, enablement, indefiniteness, and claim construction disputes involving approximate terms such as "about," "substantially," "less than," and "does not fluctuate more than 40%."

How strong is the patent estate for Rytary?

US 9,533,046 has meaningful commercial strength because it combines structural and functional limitations. A challenger must address both the formulation and the pharmacokinetic profile.

Strengths

• Three independent claims cover different formulation strategies.
• Claim 1 reaches a broad class of carboxylic acids.
• Claim 20 does not require a carboxylic acid.
• Claim 23 specifically protects tartaric-acid embodiments.
• The claims cover capsules and sprinkle administration.
• The claims include both formulation architecture and clinical pharmacokinetics.
• The patent is part of a broader continuation estate.

Vulnerabilities

• The claimed plasma profile may be vulnerable to indefiniteness or reproducibility challenges.
• The "not more than 40%" fluctuation requirement may depend heavily on sampling design and statistical treatment.
• Claim 21 gives competitors explicit dissolution targets for design-around efforts.
• Method claims may be narrower in practice than composition claims.
• The patent does not cover every extended-release carbidopa/levodopa formulation.
• A generic product can potentially avoid the acid limitations of claims 1 and 23 while targeting claim 20 separately.

The strongest enforcement position is likely against a product designed to replicate Rytary’s immediate-release plus multiple controlled-release particle architecture and its six-hour levodopa exposure profile.

How does Rytary compare with competing levodopa products?

Product	Active ingredients	Delivery format	Relation to US 9,533,046
Rytary	Carbidopa/levodopa	Immediate-release and extended-release multiparticulate capsules	Core commercial product associated with the patent family
Sinemet	Carbidopa/levodopa	Immediate-release tablets	Generally outside the multiparticulate scope
Sinemet CR	Carbidopa/levodopa	Controlled-release tablets	Different dosage-form architecture
Duopa	Carbidopa/levodopa	Continuous intestinal gel infusion	Not an oral multiparticulate formulation
Inbrija	Levodopa	Inhaled powder	Different route and active-ingredient configuration
Crexont/IPX203	Carbidopa/levodopa	Extended-release oral capsules	Competing next-generation oral delivery platform with its own patent estate

Rytary’s principal technical distinction is the combination of immediate-release and extended-release beads in a capsule. Crexont, approved by FDA in 2024, is a separate extended-release carbidopa/levodopa product and requires independent patent analysis. [5]

What generic launch scenarios exist?

Scenario 1: Paragraph III deferment

An ANDA applicant accepts the listed patent protection and defers approval until the applicable patent expiration. This reduces litigation expense but delays commercial entry.

Scenario 2: Paragraph IV challenge

The applicant argues that US 9,533,046 is invalid, not infringed, or not enforceable. The patent holder may sue within 45 days, potentially delaying approval for up to 30 months unless the litigation resolves earlier or the stay is otherwise terminated. [4]

Scenario 3: Formulation design-around

A competitor could attempt to avoid:

• the carboxylic-acid requirement in claims 1 and 23;
• the tartaric-acid requirement in claim 23;
• the two-population limitation in claim 20;
• the claim 21 dissolution profile;
• the immediate-release 1:4 carbidopa/levodopa ratio; or
• the claimed 0.5-to-six-hour plasma fluctuation range.

Avoiding one limitation may not avoid the broader Rytary estate. Continuation patents can capture alternative release coatings, particle structures, ratios, or dosing methods.

Scenario 4: Label carve-out

A section viii carve-out could remove a patented indication or dosing instruction from the generic label. The commercial value of this strategy is limited where the patented Parkinson's indication is the principal use of the product.

What manufacturing and geographic barriers apply?

The patent is a US right. It directly affects manufacture, use, sale, offers for sale, and importation into the United States under 35 U.S.C. § 271. [6] It does not independently block manufacturing in Europe, Canada, Japan, or other jurisdictions unless corresponding national patents remain in force.

The practical manufacturing barrier is reproducibility. A competitor must control:

• bead or pellet size distribution;
• coating thickness;
• acid loading and molar ratio;
• immediate-release and controlled-release dose allocation;
• dissolution performance across gastric and intestinal conditions;
• capsule filling and particle segregation; and
• batch-to-batch pharmacokinetic variability.

A process that produces the same release profile may create both patent and regulatory comparability risk even if the excipient composition differs.

What is the revenue exposure?

Rytary is the main commercial asset linked to this patent family. Revenue exposure depends on the share of branded extended-release carbidopa/levodopa sales protected by the broader patent estate, not on US 9,533,046 in isolation.

The principal loss-of-exclusivity exposure is concentrated near the reported 2029 patent-expiration period. Earlier entry remains possible through a successful Paragraph IV challenge, settlement permitting an authorized or licensed generic, or a product design that avoids the listed claims and all relevant continuation patents.

Patent value is therefore driven by:

• Rytary net sales;
• the number and scope of unexpired listed patents;
• the probability of successful generic challenge;
• the availability of a viable formulation design-around;
• the strength of any settlement restrictions; and
• the ability of a generic entrant to demonstrate bioequivalence for the multiparticulate product.

Key Takeaways

• US 9,533,046 is a method patent directed to multiparticulate carbidopa/levodopa treatment.
• Claim 1 requires a controlled-release carboxylic acid and a defined levodopa plasma profile.
• Claim 20 covers two controlled-release particle populations with different dissolution rates and does not require an acid.
• Claim 23 specifically covers tartaric-acid-containing controlled-release formulations.
• The patent claims both formulation structure and pharmacokinetic performance.
• The reported statutory expiration date is May 29, 2029.
• Rytary’s commercial exclusivity depends on the entire Orange Book and continuation-patent estate.
• Generic applicants face Paragraph IV litigation, formulation design-around, and bioequivalence risks.
• No biosimilar pathway applies because carbidopa/levodopa is a small-molecule drug.
• The principal technical design-around targets are the acid requirement, two-population structure, dissolution profile, immediate-release ratio, and plasma fluctuation limitation.

FAQs

Can a generic avoid US 9,533,046 by using tablets instead of beads?

A tablet-based product may avoid claims requiring beads, pellets, or granules, but it must also be screened against other Rytary patents and any claims that cover broader controlled-release formulations or dosing methods.

Does tartaric acid alone make a product infringing?

No. Tartaric acid is necessary for claim 23, but infringement also requires the claimed immediate-release component, controlled-release structure, dose ranges, release behavior, pharmacokinetic profile, and Parkinson's treatment use.

Can a formulation infringe if its plasma profile is not tested in every patient?

Potentially. The claims refer to a patient's plasma concentration profile and permit mean or median concentrations under dependent claims 7 and 8. The evidentiary question would depend on the product, dosing study, statistical analysis, and claim construction.

Does a six-hour dosing schedule automatically fall within the patent?

No. Claims 5, 10, and 20 address six-hour timing, but the formulation and pharmacokinetic limitations also must be satisfied. A six-hour administration interval alone is insufficient.

Is US 9,533,046 relevant to Crexont?

It may be relevant to an overlap analysis because both products use oral extended-release carbidopa/levodopa technologies, but Crexont must be evaluated against its own formulation, labeling, Orange Book listings, and patent family. Product similarity does not establish infringement.

References

1. United States Patent and Trademark Office. (2017). U.S. Patent No. 9,533,046, multiparticulate formulations of levodopa and carbidopa.
2. U.S. Food and Drug Administration. (2015). Rytary approval letter and prescribing information, NDA 204630.
3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
4. Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 355(j).
5. U.S. Food and Drug Administration. (2024). FDA approves extended-release carbidopa and levodopa capsules for Parkinson's disease.
6. Patent Act, 35 U.S.C. § 271.

Drugs Protected by US Patent 9,533,046

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Impax	RYTARY	carbidopa; levodopa	CAPSULE, EXTENDED RELEASE;ORAL	203312-001	Jan 7, 2015		RX	Yes	No	9,533,046		Y			TREATMENT OF PARKINSON'S DISEASE
Impax	RYTARY	carbidopa; levodopa	CAPSULE, EXTENDED RELEASE;ORAL	203312-002	Jan 7, 2015		RX	Yes	No	9,533,046		Y			TREATMENT OF PARKINSON'S DISEASE
Impax	RYTARY	carbidopa; levodopa	CAPSULE, EXTENDED RELEASE;ORAL	203312-003	Jan 7, 2015		RX	Yes	No	9,533,046		Y			TREATMENT OF PARKINSON'S DISEASE
Impax	RYTARY	carbidopa; levodopa	CAPSULE, EXTENDED RELEASE;ORAL	203312-004	Jan 7, 2015		RX	Yes	Yes	9,533,046		Y			TREATMENT OF PARKINSON'S DISEASE

International Family Members for US Patent 9,533,046

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2008343787
Canada	2711014
China	101910113
European Patent Office	2234963
Spain	2804348
Israel	206756