Details for Patent: 12,178,919

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Which drugs does patent 12,178,919 protect, and when does it expire?

Patent 12,178,919 protects CREXONT and is included in one NDA.

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

Summary for Patent: 12,178,919

Title:	Muco-adhesive, controlled release formulation of levodopa and/or esters of levodopa and uses thereof
Abstract:	The invention provides an oral solid formulation comprising (a) a controlled release component comprising a core comprising levodopa, wherein the core is coated with a muco-adhesive coating and the muco-adhesive coating is externally coated with an enteric coating; and (b) an immediate release component comprising levodopa. The invention further provides a method for making and using the oral solid formulation.
Inventor(s):	Ann Hsu, Liang Dong, Amy Ding, Suneel Gupta
Assignee:	Impax Laboratories LLC
Application Number:	US18/791,632
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 12,178,919
Patent Claim Types: see list of patent claims	Use; Formulation; Dosage form;

US Patent 12,178,919: Levodopa Multiparticulate Controlled-Release Formulation Patent Analysis

US Patent 12,178,919 protects a multiparticulate levodopa formulation that combines an immediate-release levodopa/decarboxylase-inhibitor component with a separate controlled-release levodopa component. The broadest claims require the formulation to be free of a pH-adjusting carboxylic acid. Dependent claims add asymmetric drug distribution, coated bead architecture, mucoadhesive polymers, particle-size parameters, pharmacokinetic performance, and Parkinson's disease treatment methods.

The patent is potentially relevant to extended-release carbidopa/levodopa products using immediate-release granules and controlled-release beads, including formulations positioned to provide rapid levodopa onset followed by sustained exposure.

What does US Patent 12,178,919 claim?

The patent has three principal claim groups:

Claim group	Claims	Protected subject matter
Composition claims	1-21	Multiparticulate controlled-release levodopa formulations
Pharmacokinetic composition claims	13-15	Formulations meeting specified levodopa plasma-concentration timing
Method-of-treatment claims	22-23	Oral treatment of Parkinson's disease or primary Parkinsonism

The independent claims are claims 1, 13, 16, and 22.

Claim 1: broad formulation architecture

Claim 1 requires all of the following:

1. An immediate-release component containing levodopa, an ester or salt of levodopa, and a decarboxylase inhibitor.
2. A controlled-release component containing a core with levodopa, an ester or salt of levodopa.
3. The overall formulation is free of a pH-adjusting carboxylic acid.

The claim does not require the controlled-release component to contain a decarboxylase inhibitor. Claim 2 expressly narrows the formulation by requiring that component to be free of the inhibitor.

The claim is composition-focused. It does not require a specific dosage strength, levodopa-to-carbidopa ratio, release percentage, bead size, coating thickness, excipient concentration, or clinical indication.

Claim 13: pharmacokinetic limitation

Claim 13 adds a functional performance requirement. After oral administration under fasting conditions, the formulation must:

• reach 50% of maximum levodopa plasma concentration within one hour; and
• maintain that 50% Cmax concentration for at least about three hours.

Claim 14 extends the maintenance period to at least about five hours.

These claims create potential infringement disputes centered on clinical or pharmacokinetic testing. A product could have a similar formulation architecture but avoid claims 13 and 14 if it does not satisfy the stated plasma-concentration profile. The reverse is also possible: a product with different manufacturing details could face risk if it meets the functional limitations and the structural limitations of claim 13.

Claim 16: granular and bead-core structure

Claim 16 requires:

• immediate-release granules containing levodopa and a decarboxylase inhibitor; and
• controlled-release spheronized bead cores containing levodopa or a levodopa salt or ester; and
• no pH-adjusting carboxylic acid.

This claim is narrower structurally than claim 1 because it specifies granules for the immediate-release portion and spheronized bead cores for the controlled-release portion. It may be particularly relevant to products manufactured through wet granulation, extrusion-spheronization, layering, or related multiparticulate processes.

Claim 22: treatment method

Claim 22 covers oral administration of the claimed multiparticulate formulation to treat Parkinson's disease or primary Parkinsonism.

The method claim incorporates the principal composition limitations from claim 1. It therefore requires the same two-part formulation architecture and the absence of a pH-adjusting carboxylic acid.

Which formulation features are required for infringement?

A product must satisfy every limitation of an asserted claim. The core limitations are:

Limitation	Claims affected	Commercial significance
Immediate-release levodopa plus decarboxylase inhibitor	1, 13, 16, 22	Requires early exposure from a combination component
Separate controlled-release levodopa component	1, 13, 16, 22	Excludes a simple single-phase extended-release tablet
Controlled-release component may lack inhibitor	2, 15, 21, 23	Protects asymmetric distribution of carbidopa or another inhibitor
No pH-adjusting carboxylic acid	1-23, as incorporated	Important formulation-design limitation
Mucoadhesive coating	4, 7-10, 17-20	Protects gastrointestinal adhesion strategy
Controlled-release coating under mucoadhesive layer	5, 6, 18, 19	Protects multilayer bead construction
Ethyl cellulose or cellulose acetate	6, 19	Narrows the coating-material scope
Positively charged gastrointestinal mucoadhesive polymer	7, 20	Functional polymer limitation
Amino methacrylate copolymer	8-9	Points to Eudragit-type amino methacrylate chemistry
Enteric outer coating	10	Protects an additional pH-responsive coating layer
Particle-size screen limitations	11-12	Adds manufacturing and particle-distribution constraints
50% Cmax within one hour and maintained three to five hours	13-14	Creates pharmacokinetic infringement test
Spheronized bead cores and immediate-release granules	16-21	Protects a specific multiparticulate manufacturing format

How broad is the “free of a pH-adjusting carboxylic acid” limitation?

This limitation is central to the patent.

The claims do not broadly require the formulation to be free of every carboxylic acid. They require the formulation to be free of a pH-adjusting carboxylic acid. The legal issue is therefore whether a particular acid is present for pH adjustment or another formulation function.

Potentially relevant compounds could include citric acid, fumaric acid, malic acid, tartaric acid, succinic acid, adipic acid, or related acidic excipients. Their presence would not automatically establish infringement or noninfringement. The analysis would depend on:

• the identity and concentration of the acid;
• its stated formulation purpose;
• whether it materially adjusts microenvironmental or gastrointestinal pH;
• manufacturing documents and product specifications;
• regulatory descriptions of the excipient;
• expert evidence concerning the formulation's pH behavior.

A generic applicant could target this limitation by using a formulation containing a qualifying pH-adjusting carboxylic acid. That strategy would carry litigation risk if the patent holder argues that the acid is not pH-adjusting, is present only incidentally, or that the product infringes under a broader claim construction.

What coatings and polymers are protected?

Mucoadhesive coating

Claims 4 and 17 require a mucoadhesive coating over the controlled-release core or spheronized bead core.

Claims 7 and 20 narrow the coating to a polymer capable of forming a positive ionic charge at a pH present in the human gastrointestinal tract. Claims 8 and 9 specifically identify amino methacrylate copolymers, including:

• poly(butyl methacrylate-co-(2-dimethylaminoethyl)methacrylate-co-methylmethacrylate).

This chemistry corresponds to cationic amino methacrylate polymers commonly used in pharmaceutical coatings. The claims focus on charge behavior in the gastrointestinal environment rather than merely requiring a named commercial excipient.

Controlled-release undercoat

Claims 5, 6, 18, and 19 require a controlled-release coating beneath the mucoadhesive coating. The specified materials are:

• ethyl cellulose;
• cellulose acetate; or
• mixtures of those materials.

The layering sequence matters. A product with an ethyl-cellulose coating above a mucoadhesive coating would not literally satisfy a claim requiring the controlled-release coating to undercoat the mucoadhesive coating, subject to claim construction and equivalents analysis.

Enteric outer layer

Claim 10 adds an enteric coating surrounding the mucoadhesive coating. This produces a three-level architecture:

1. levodopa bead core;
2. controlled-release coating;
3. mucoadhesive coating;
4. enteric outer coating.

The claim does not identify one specific enteric polymer. A formulation using a methacrylic acid copolymer, cellulose acetate phthalate, hypromellose phthalate, or another enteric material could potentially fall within the claim if the remaining limitations are met.

How does the patent allocate levodopa and the decarboxylase inhibitor?

The patent protects an asymmetric distribution in which the immediate-release component contains the decarboxylase inhibitor while the controlled-release component may contain levodopa alone.

Claim 3 requires the immediate-release component to contain approximately 80% to 100% of the total decarboxylase inhibitor in the formulation. Claims 2, 15, 21, and 23 go further by requiring that the controlled-release component be free of the inhibitor.

This architecture may have commercial value because it separates the rapid-release inhibitor dose from the sustained-release levodopa dose. The claims therefore reach beyond conventional co-formulation concepts that place levodopa and carbidopa together in every dosage fraction.

The term “decarboxylase inhibitor” is not limited in the provided claims to carbidopa. Depending on the specification and applicable claim construction, the category could potentially include benserazide or another peripheral aromatic L-amino-acid decarboxylase inhibitor. Product-specific analysis would depend on the patent's specification and prosecution history.

What are the particle-size limitations?

Claims 11 and 12 address screen retention and passage:

• Claim 11 requires the controlled-release component to pass through a number 12, 14, and/or 16 mesh screen.
• Claim 12 requires it to be retained on a number 18, 24, and/or 25 mesh screen.

These limitations appear directed to multiparticulate bead or granule size. The claim language uses alternative screen sizes, which may create construction issues concerning whether one listed screen is sufficient or whether the component must satisfy a defined combination of screens.

Particle-size claims can be difficult to assess from public labeling alone. Relevant evidence would include:

• sieve analysis;
• batch-release specifications;
• manufacturing records;
• particle-size distribution data;
• retained samples;
• regulatory chemistry, manufacturing, and controls submissions.

A generic manufacturer may need to design around the claimed particle range or maintain evidence that its controlled-release particles do not meet the relevant screen limitations.

What pharmacokinetic performance does the patent protect?

Claims 13 and 14 are unusual because they combine structural formulation requirements with a plasma-concentration profile.

The claimed profile requires rapid attainment of half of maximum levodopa concentration, followed by maintenance of that exposure level:

Parameter	Claim 13	Claim 14
Administration condition	Oral, fasting	Oral, fasting
Time to 50% Cmax	Within one hour	Within one hour
Duration at or above 50% Cmax	At least about three hours	At least about five hours

The claims do not specify:

• dose size;
• number of subjects;
• study design;
• sampling intervals;
• statistical treatment;
• whether “maintained” means continuously above the threshold;
• whether the analysis applies to individual subjects or mean plasma concentrations.

Those issues may become material in litigation. The patent holder would likely rely on pharmacokinetic studies, while an accused party could challenge the reproducibility, statistical meaning, or measurement protocol used to establish the limitation.

What generic entry risks exist?

A generic or follow-on product faces the highest risk if it combines:

• immediate-release levodopa/carbidopa granules;
• extended-release levodopa beads;
• cationic mucoadhesive coating;
• ethyl cellulose or cellulose acetate release coating;
• no pH-adjusting carboxylic acid;
• a particle-size distribution within the claimed range.

Risk is lower where the product uses one or more of the following design differences:

• a single-phase tablet rather than multiparticulates;
• levodopa and carbidopa in both immediate- and controlled-release fractions;
• a controlled-release component containing a carboxylic-acid pH modifier;
• a nonmucoadhesive coating;
• an anionic or neutral polymer rather than a positively charged amino methacrylate polymer;
• a coating sequence different from the claimed order;
• non-spheronized controlled-release particles;
• a pharmacokinetic profile outside the claimed thresholds.

A Paragraph IV certification would require an applicant to address listed patents that claim the reference drug, its formulation, or an approved method of use. The supplied claim text does not establish whether US 12,178,919 is listed in the FDA Orange Book, which product it covers, or whether a Paragraph IV notice has been served.

What is the Orange Book and FDA status of US 12,178,919?

The claim text alone does not establish Orange Book listing status. Patent eligibility for listing depends on whether the patent claims an approved drug substance, drug product, or method of use and whether the patent was submitted in accordance with FDA listing requirements.

The relevant regulatory questions are:

Issue	Determination from the supplied information
FDA-approved product covered	Not established
Orange Book listing	Not established
Listed drug application number	Not established
Paragraph IV certification	Not established
30-month stay	Not established
New chemical entity exclusivity	Not established
Three-year approval exclusivity	Not established
Pediatric exclusivity	Not established

The formulation appears technically aligned with an extended-release levodopa/carbidopa product, but technical similarity does not prove regulatory linkage. Orange Book status must be confirmed from the current FDA publication and the relevant approved labeling.

What is the patent term and expiration date?

The issue date and expiration date cannot be determined reliably from the claims alone. The effective expiration date would depend on:

• the earliest effective nonprovisional priority date;
• any terminal disclaimer;
• patent term adjustment;
• patent term extension;
• continuity data;
• disclaimers or post-grant proceedings.

For a US utility patent filed after June 8, 1995, the ordinary term is generally 20 years from the earliest effective nonprovisional filing date, subject to adjustments and extensions under 35 U.S.C. §§ 154 and 156. A reliable expiration calculation requires the patent's front-page priority data, continuity statement, USPTO Patent Center record, and any terminal-disclaimer information.

How strong is the patent estate based on the claims?

The patent has meaningful formulation coverage but its practical strength is concentrated in specific combinations.

Strength factor	Assessment
Broad composition concept	Moderate
Asymmetric inhibitor distribution	Stronger
Mucoadhesive and controlled-release layering	Stronger
Specific amino methacrylate polymer	Narrow but technically concrete
Pharmacokinetic claims	Potentially valuable but evidence-intensive
Method-of-treatment claims	Dependent on formulation use and approved indication
Particle-size claims	Potentially difficult to detect without discovery
No-carboxylic-acid limitation	Provides a clear design-around path
Manufacturing-process coverage	Limited in the supplied claims
Active-ingredient coverage	Levodopa-centered and formulation-specific

The independent claims do not broadly cover all controlled-release levodopa/carbidopa products. They require a multiparticulate system with immediate-release and controlled-release populations. The strongest infringement theory would likely involve a product that intentionally reproduces the claimed bead-and-granule architecture.

Which competing products are most relevant?

The closest commercial comparator is an extended-release carbidopa/levodopa product using combined immediate- and extended-release delivery. Rytary, marketed by Amneal Pharmaceuticals, is the principal US reference product in this category. Crexont, also marketed by Amneal, is a newer extended-release carbidopa/levodopa product using an immediate-release and extended-release formulation approach.

Product	Active ingredients	Broad dosage concept	Relevance to patent
Sinemet	Levodopa/carbidopa	Immediate-release tablets and other forms	Lower formulation similarity
Sinemet CR	Levodopa/carbidopa	Controlled-release tablet	Lower multiparticulate similarity
Rytary	Levodopa/carbidopa	Extended-release capsules with multiparticulate delivery	High technical relevance
Crexont	Levodopa/carbidopa	Immediate- and extended-release formulation	High technical relevance
Duopa	Levodopa/carbidopa	Intestinal gel infusion	Low relevance to oral multiparticulate claims
Generic ER products	Levodopa/carbidopa	Product-specific	Depends on formulation architecture

Commercial similarity does not establish infringement. The decisive facts are the product's detailed formulation, coating sequence, excipient composition, particle-size distribution, and pharmacokinetic performance.

What licensing and litigation issues should be monitored?

The supplied information does not establish a license, settlement, infringement complaint, Paragraph IV notice, or court judgment involving US 12,178,919.

For commercial diligence, the relevant records are:

• USPTO Patent Center for prosecution and terminal disclaimers;
• FDA Orange Book patent listings;
• FDA Paragraph IV litigation reports;
• PACER and district-court dockets;
• ANDA litigation complaints under the Hatch-Waxman Act;
• licensing and collaboration disclosures by the patent owner and product sponsor;
• SEC filings identifying royalty obligations, patent disputes, or exclusivity arrangements.

The patent's commercial exposure is greatest if it is listed against a high-volume extended-release levodopa/carbidopa product. Its value is lower if it is unlisted, not tied to an approved product, or limited to a development formulation that is not commercially deployed.

Key Takeaways

• US Patent 12,178,919 targets multiparticulate levodopa delivery, not all controlled-release levodopa products.
• The central architecture combines immediate-release levodopa plus a decarboxylase inhibitor with a separate controlled-release levodopa component.
• The controlled-release component may be free of the decarboxylase inhibitor, creating asymmetric drug distribution.
• The principal formulation distinction is the absence of a pH-adjusting carboxylic acid.
• Dependent claims protect mucoadhesive coatings, cationic amino methacrylate polymers, ethyl cellulose or cellulose acetate, enteric layers, bead-size parameters, and spheronized cores.
• Claims 13 and 14 add a pharmacokinetic profile requiring rapid levodopa exposure and maintenance for three to five hours.
• The most relevant competitive products are extended-release carbidopa/levodopa products using multiparticulate delivery, particularly Rytary and Crexont.
• The supplied claim text does not establish Orange Book listing, Paragraph IV activity, patent expiration, licensing, settlement, or litigation status.
• The most practical design-around paths involve changing the dosage architecture, distributing the decarboxylase inhibitor into the controlled-release fraction, using a pH-adjusting carboxylic acid, eliminating the claimed mucoadhesive layer, or altering the coating sequence.

FAQs About US Patent 12,178,919

Does US Patent 12,178,919 cover Rytary?

The claims are technically relevant to an extended-release levodopa/carbidopa product using immediate-release and controlled-release multiparticulates. The claim text alone does not establish whether Rytary practices the claims or whether the patent is listed for Rytary.

Does US Patent 12,178,919 cover Crexont?

Crexont is commercially relevant because it uses an immediate- and extended-release carbidopa/levodopa delivery approach. Infringement would depend on the confidential and public formulation details, including coatings, excipients, bead structure, particle size, and the absence or presence of a pH-adjusting carboxylic acid.

Can a generic avoid the patent by placing carbidopa in the controlled-release beads?

That may avoid claims requiring the controlled-release component to be free of the decarboxylase inhibitor. It would not necessarily avoid claim 1, which does not require the controlled-release component to exclude the inhibitor, provided all other claim limitations are met.

Does the patent cover a conventional extended-release tablet?

The supplied claims require a multiparticulate formulation. A conventional monolithic extended-release tablet would generally have a stronger noninfringement position against the composition claims, subject to the product's actual structure and any applicable equivalents analysis.

Is the patent vulnerable because “about” is used in the pharmacokinetic claims?

The terms “about,” “within one hour,” and “at least about” may create claim-construction and enablement issues, but they do not automatically invalidate the claims. Their effect depends on the specification, prosecution history, experimental data, and the court's construction of the pharmacokinetic limitations.

Sources

1. United States Patent and Trademark Office. (2024). U.S. Patent No. 12,178,919.
2. United States Code, 35 U.S.C. §§ 154, 156.
3. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book.
4. U.S. Food and Drug Administration. (n.d.). Approved drug product labeling for carbidopa and levodopa extended-release products.

Drugs Protected by US Patent 12,178,919

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	CREXONT	carbidopa; levodopa	CAPSULE, EXTENDED RELEASE;ORAL	217186-001	Aug 7, 2024		RX	Yes	No	12,178,919		Y			TREATMENT OF PARKINSON'S DISEASE
Impax	CREXONT	carbidopa; levodopa	CAPSULE, EXTENDED RELEASE;ORAL	217186-002	Aug 7, 2024		RX	Yes	No	12,178,919		Y			TREATMENT OF PARKINSON'S DISEASE
Impax	CREXONT	carbidopa; levodopa	CAPSULE, EXTENDED RELEASE;ORAL	217186-003	Aug 7, 2024		RX	Yes	No	12,178,919		Y			TREATMENT OF PARKINSON'S DISEASE
Impax	CREXONT	carbidopa; levodopa	CAPSULE, EXTENDED RELEASE;ORAL	217186-004	Aug 7, 2024		RX	Yes	Yes	12,178,919		Y			TREATMENT OF PARKINSON'S DISEASE

International Family Members for US Patent 12,178,919

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2014332024
Australia	2019284060
Australia	2021282393
Canada	2926082