Details for Patent: 12,201,596

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Which drugs does patent 12,201,596 protect, and when does it expire?

Patent 12,201,596 protects CREXONT and is included in one NDA.

This patent has seven patent family members in seven countries.

Summary for Patent: 12,201,596

Title:	Levodopa dosing regimen
Abstract:	The invention is a method for treating patients with post-encephalitic parkinsonism, parkinsonism that may follow carbon monoxide intoxication, or parkinsonism that may follow manganese intoxication by orally administering a controlled release levodopa formulation and the method provides an improvement of a patient's total post-dose “Off” time compared to post-dose of treatment regimens with oral immediate release levodopa tablets.
Inventor(s):	Richard D'Souza, Hester Visser, Suneel Gupta
Assignee:	Amneal Pharmaceuticals LLC
Application Number:	US18/823,153
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 12,201,596
Patent Claim Types: see list of patent claims	Use; Dosage form;

United States Patent 12,201,596: Levodopa Multiparticulate Formulation, Claim Scope, and Patent Landscape

U.S. Patent 12,201,596 covers patient-specific conversion from frequent immediate-release levodopa dosing to twice- or thrice-daily multiparticulate controlled-release levodopa/carbidopa. The claims require a defined patient population, a 2.8-fold per-dose levodopa conversion in the broadest independent claim, specific bead architecture, and at least a 5% reduction in post-dose “Off” time. The patent is directed to a method of treatment rather than a standalone composition.

The claims are closely aligned with the clinical and formulation characteristics of Amneal Pharmaceuticals’ IPX203 product, marketed as Crexont. Because the patent claims a treatment method and the product is a small-molecule drug, the principal commercial risks are generic Paragraph IV challenges and formulation or method-of-use workarounds, not biosimilar substitution.

What does U.S. Patent 12,201,596 cover?

Patent 12,201,596 covers a treatment protocol for Parkinson’s disease using a multiparticulate controlled-release levodopa dosage form containing immediate-release levodopa/carbidopa and controlled-release levodopa beads.

The core elements are:

Claim element	Requirement
Disease	Parkinson’s disease
Claimed etiologies	Post-encephalitic parkinsonism; parkinsonism following carbon monoxide intoxication; or parkinsonism following manganese intoxication
Prior treatment	Immediate-release levodopa tablets administered three, four, five, or more times daily
Prior daily dose	500 mg of levodopa or less in claim 1
Conversion	Immediate-release treatment is discontinued
New treatment	Multiparticulate controlled-release levodopa dosage form administered twice or three times daily
Dose conversion	Each new dose contains 2.8 times the prior per-administration levodopa amount in claim 1
Formulation	Controlled-release levodopa components plus an immediate-release levodopa/carbidopa component
Clinical result	At least a 5% decrease in total post-dose “Off” time
Controlled-release structure	Levodopa core, mucoadhesive polymer layer, and external enteric coating
Optional parameters	Bead size, dissolution profile, plasma concentration, fluctuation index, and titration schedule

The patent does not claim every controlled-release levodopa product. Infringement requires satisfaction of the claimed patient-selection, dose-conversion, formulation, administration, and clinical-outcome limitations.

How are the independent claims structured?

Claim 1: Broadest conversion protocol

Claim 1 is the principal broad method claim. It requires:

1. Selection of a patient in one of three specified parkinsonism subgroups.
2. Prior use of immediate-release levodopa tablets three or more times daily.
3. A total daily immediate-release levodopa dose of 500 mg or less.
4. Determination of the amount administered per immediate-release dose.
5. Discontinuation of the immediate-release tablets.
6. Administration of the multiparticulate controlled-release product twice or three times daily.
7. A new per-administration levodopa amount equal to 2.8 times the prior per-administration amount.
8. At least a 5% decrease in post-dose “Off” time.
9. The claimed bead and immediate-release formulation architecture.

The 2.8-fold conversion is a major limiting feature. A generic applicant using a fixed dose conversion, weight-based dosing, pharmacokinetic modeling, or a ratio materially different from 2.8 times the prior dose may create noninfringement arguments. The strength of that argument would depend on claim construction, prosecution history, and whether the accused dosing instruction nevertheless performs the same claimed calculation.

Claim 10: Fixed 280-mg conversion

Claim 10 narrows the population and prior dosing regimen. It requires:

• Four- or five-times-daily immediate-release tablets.
• Each prior dose containing 100 mg of levodopa.
• A new capsule regimen administered twice or three times daily.
• Each administration containing 280 mg of levodopa.
• The claimed controlled-release beads and immediate-release levodopa/carbidopa component.
• At least a 5% reduction in post-dose “Off” time.

This claim captures the practical conversion from 100 mg immediate-release levodopa doses to 280 mg levodopa per controlled-release administration. It is narrower than claim 1 but potentially more straightforward to prove where labeling or prescribing instructions expressly identify the 280-mg dose.

Claim 14: Fixed 280-mg twice-daily regimen

Claim 14 is narrower than claim 10 because it requires administration twice daily rather than twice or three times daily. The claim otherwise tracks claim 10.

A twice-daily product label or conversion protocol that satisfies the remaining limitations would present a direct method-of-use risk if the claimed patient population and clinical result are also met.

What formulation is protected by Patent 12,201,596?

The formulation has two functional populations of particles or components:

1. Controlled-release levodopa components.
2. An immediate-release component containing levodopa and carbidopa.

The controlled-release component requires a layered structure:

1. A levodopa-containing core.
2. A mucoadhesive polymer layer coating the core.
3. An external enteric coating polymer.

Claims 3, 11, and 15 add a rate-controlling polymer layer beneath the mucoadhesive layer. Claims 4, 12, and 16 require the controlled-release components to be beads. Claims 5, 13, and 17 further define bead size by screen retention.

What capsule strengths are claimed?

Claim 2 identifies four capsule strengths:

Levodopa	Carbidopa
140 mg	35 mg
210 mg	52.5 mg
280 mg	70 mg
350 mg	87.5 mg

The levodopa-to-carbidopa ratio is 4:1 in each strength. The claim permits one or a combination of the listed capsules per dosing time.

The 280 mg/70 mg strength is separately central to claims 10 and 14. That limitation may be commercially important because a product can avoid certain fixed-dose claims by using a different strength, although claims 1 and 2 may still present exposure depending on the actual dosing instructions and formulation.

What technical parameters are required by the dependent claims?

Bead size

Claims 5, 13, and 17 require beads that:

• Pass through 12-, 14-, and 16-mesh screens; and
• Are retained on 18-, 20-, or 24-mesh screens.

This defines a particle-size range rather than a single diameter. The effective size depends on the applicable mesh convention and test method. A generic developer could seek a formulation outside the claimed screen range, but particle-size control would need to remain compatible with manufacturing, dissolution, dose uniformity, and gastrointestinal performance.

Dissolution profile

Claim 6 requires testing in USP Apparatus I at 75 rpm and 37°C ± 0.5°C, using 500 to 900 mL of simulated gastric fluid for two hours followed by pH 6.8 phosphate buffer. The release limits are:

Time	Levodopa released
2 hours	20% to 60%
3 hours	40% to 80%
4 hours	60% to 100%
7 hours	At least 80%

The claim uses overlapping cumulative-release ranges. A product that falls outside one range may avoid claim 6 while remaining within claims 1, 10, or 14 if the other structural and treatment limitations are met.

Plasma concentration

Claim 7 requires a levodopa plasma concentration of approximately 200 to 2,000 ng/mL within 0.25 to one hour after administration. This is a product-performance limitation that may require pharmacokinetic evidence. It is unlikely to be resolved solely from the label unless the applicant’s clinical or product data disclose the parameter.

Fluctuation index

Claim 8 requires a levodopa fluctuation index of approximately 1.7 ± 0.5 hours. The term may become disputed if the patent specification or prosecution history does not define the calculation method sufficiently. A generic challenger could contest both infringement and validity based on measurement reproducibility and written-description support.

Initial twice-daily titration

Claim 9 requires an initial twice-daily regimen for one to nine days, followed by thrice-daily administration. This claim targets a specific transition schedule. A label that begins with thrice-daily dosing, or uses a titration period outside the stated range, may avoid claim 9.

How strong is the patent estate for Crexont and IPX203?

Patent 12,201,596 is one component of the IPX203/Crexont estate. The broader estate has included formulation and treatment-method patents associated with multiparticulate levodopa/carbidopa delivery. Public FDA and patent records should be read together because patent protection may include both Orange Book-listed patents and related family members that are not listed for every regulatory presentation.

Estate category	Commercial relevance
Multiparticulate formulation patents	Protect bead architecture, polymer layers, release behavior, and particle size
Method-of-treatment patents	Protect conversion from immediate-release levodopa to controlled-release dosing
Dose-regimen claims	Protect fixed 280-mg dosing, twice-daily use, and twice-to-thrice-daily conversion
Pharmacokinetic claims	Protect plasma concentration and fluctuation characteristics
Manufacturing claims	May protect coating sequence, bead production, polymer application, and release control
Regulatory listings	Can delay approval of an ANDA that references the listed product

The strongest practical claims are likely claims 1, 10, and 14 because they combine the clinical conversion protocol with the formulation structure. The dependent claims add attack surfaces but also create fallback positions if a court narrows the independent claims.

The weakest individual limitations from an enforcement perspective may be the unusual patient-etiology requirement and the post-dose “Off” time reduction. Those elements can create proof problems if the accused generic label does not expressly instruct treatment of those subgroups or measure the specified outcome.

What is the Orange Book status of Patent 12,201,596?

Crexont received FDA approval in August 2024 for carbidopa and levodopa extended-release capsules for the treatment of Parkinson’s disease, including associated “Off” episodes in patients previously treated with immediate-release carbidopa/levodopa. The FDA approval established the product as a reference-listed drug for ANDA purposes.[1]

The relevant regulatory questions are:

• Whether Patent 12,201,596 is listed for the approved Crexont strength and dosage form.
• Whether the listing is categorized as a formulation, method-of-use, or product-by-process patent.
• Whether the listed claims correspond to an approved labeling indication.
• Whether the patent has a pediatric extension, patent-term adjustment, or terminal disclaimer.
• Whether the Orange Book listing includes a use code that can be carved out through a section viii statement.

A method claim directed to narrow etiologies such as post-encephalitic, carbon-monoxide-related, or manganese-related parkinsonism may be vulnerable to a section viii carve-out if that use is not required by the approved label. A formulation claim generally presents a more direct ANDA certification issue because the generic product itself may practice the claimed structure.

When does Patent 12,201,596 lose exclusivity?

The patent’s expiration date cannot be determined from the claims alone. The operative date depends on the patent’s earliest effective nonprovisional filing date, patent-term adjustment, terminal disclaimers, and any patent-term extension. The patent number and claim text do not establish those dates.

The statutory framework is:

• Utility patents generally expire 20 years from the earliest effective nonprovisional filing date under 35 U.S.C. § 154.
• Patent-term adjustment may extend the term for USPTO delay.
• A terminal disclaimer can limit a continuation’s term to the expiration of an earlier patent.
• FDA regulatory exclusivity is separate from patent term.
• Any Hatch-Waxman patent-term extension must be confirmed through FDA and USPTO records.

For investment and launch modeling, the relevant exclusivity date should be taken from the current Orange Book entry and the USPTO patent record, not inferred from the issue date.

Which companies are challenging the Crexont patent estate?

Crexont is a small-molecule product. It therefore faces ANDA-based generic competition rather than biosimilar competition under the Public Health Service Act.

A Paragraph IV challenge would require a generic applicant to certify that a listed patent is invalid, unenforceable, or not infringed. If the NDA holder sues within 45 days of receiving a Paragraph IV notice, FDA approval may be subject to a 30-month stay under 21 U.S.C. § 355(j)(5)(B)(iii), subject to statutory exceptions.

No confirmed challenger, complaint, settlement, or court judgment can be attributed to Patent 12,201,596 from the claim text supplied. A definitive litigation analysis requires the current FDA Orange Book, Federal Court docket records, and any Abbreviated New Drug Application litigation notices.

What generic launch risks exist?

At-risk launch

A generic manufacturer could launch before patent expiry if it concludes that the listed claims are invalid or not infringed. This creates exposure to preliminary-injunction proceedings and damages.

Label carve-out

A generic applicant may attempt to omit protected methods of use through a section viii statement. This strategy is more plausible for claims requiring the three unusual Parkinsonism etiologies or a specific “Off” time reduction than for claims directed to the formulation itself.

Formulation redesign

Potential design-around approaches include:

• Replacing the mucoadhesive polymer.
• Eliminating the external enteric coating.
• Using a non-bead multiparticulate system.
• Changing the particle-size distribution.
• Using a different controlled-release mechanism.
• Altering the immediate-release and controlled-release fractions.
• Using a dose-conversion instruction that does not state 2.8 times the prior dose.
• Avoiding the claimed dissolution profile.

Each approach carries performance and regulatory risks. A formulation that avoids literal infringement may still face doctrine-of-equivalents arguments, although prosecution-history estoppel and the specificity of the layered structure could limit that risk.

What manufacturing and IP barriers affect generic entry?

The manufacturing barrier is higher than for a conventional immediate-release tablet. A competing product must control:

• Levodopa loading in the core.
• Application of the mucoadhesive polymer.
• Application of any rate-controlling undercoat.
• Application and curing of the enteric layer.
• Bead-size distribution.
• Immediate-release levodopa/carbidopa blending.
• Capsule fill weight and dose uniformity.
• Release in acidic and buffered media.
• Stability of levodopa, which is susceptible to degradation and oxidation.

The patent’s layered bead architecture creates a technical barrier even if a generic applicant ultimately designs around the literal claims. Bioequivalence may require a product with comparable exposure and food-effect behavior, while a different release mechanism could trigger additional FDA development work.

How does Patent 12,201,596 compare with Rytary patents?

Rytary is an extended-release carbidopa/levodopa capsule using an extended-release multiparticulate technology. Crexont/IPX203 also relies on multiparticulate delivery but is associated with a distinct product and patent estate.

Issue	Patent 12,201,596 / Crexont	Rytary
Active ingredients	Levodopa and carbidopa	Levodopa and carbidopa
Dosage form	Capsule with multiparticulate components	Extended-release capsule with multiparticulate components
Claimed conversion	Express 2.8-fold per-dose conversion in claim 1	Product-specific conversion instructions
Clinical endpoint	At least 5% reduction in post-dose “Off” time	Label-specific control of motor fluctuations
Structural limitation	Mucoadhesive and enteric-coated levodopa components	Separate formulation and patent family
Regulatory pathway	NDA and ANDA framework	NDA and ANDA framework
Biosimilar risk	None	None
Main competitive risk	Formulation and method-of-use Paragraph IV litigation	Formulation, method-of-use, and patent-expiry timing

The existence of Rytary patents does not by itself establish freedom to operate for Crexont or a generic competitor. Each product requires a separate claim chart covering polymer identity, layer order, release kinetics, particle size, capsule contents, and labeling.

What is the commercial exposure from patent protection?

Crexont entered the market as an extended-release alternative for patients receiving frequent immediate-release carbidopa/levodopa dosing. Its commercial value depends on:

• Conversion of patients with motor fluctuations.
• Reduction in dosing frequency.
• Retention of patients on branded extended-release therapy.
• The number of capsules required per dosing event.
• Prescriber acceptance of the conversion algorithm.
• Generic access to either the formulation or the active-ingredient combination.
• The timing of ANDA approvals after listed-patent challenges.

Patent 12,201,596 has greater relevance to commercial conversion protocols than to every possible levodopa formulation. The formulation limitations and unusual patient-selection language divide the risk: formulation claims can create product-level exposure, while method claims may be avoidable through labeling or dosing design.

Key Takeaways

1. Patent 12,201,596 claims a method of converting selected Parkinson’s patients from frequent immediate-release levodopa to twice- or thrice-daily multiparticulate controlled-release levodopa/carbidopa.
2. Claim 1 requires a 2.8-fold increase in levodopa per administration and at least a 5% reduction in post-dose “Off” time.
3. Claims 10 and 14 focus on conversion from four- or five-times-daily 100-mg levodopa doses to 280 mg per administration.
4. The claimed formulation uses levodopa cores, mucoadhesive polymer layers, external enteric coatings, and an immediate-release levodopa/carbidopa component.
5. The patent includes additional protection for rate-controlling undercoats, bead size, dissolution, plasma concentration, fluctuation index, and titration.
6. Crexont is a small-molecule product, so the relevant competitive pathway is ANDA litigation and Paragraph IV certification, not biosimilar litigation.
7. The narrow Parkinsonism etiologies may create label-carve-out and proof-of-infringement issues.
8. The formulation claims create the principal product-level barrier because a generic may practice them regardless of how its label describes the treatment method.
9. Patent expiry must be confirmed from the USPTO and current Orange Book records because the claims do not establish patent-term adjustment, terminal disclaimer, or extension data.
10. A complete freedom-to-operate analysis requires claim charts against the actual generic formulation, capsule composition, dissolution profile, manufacturing process, and proposed label.

FAQs

Does Patent 12,201,596 cover all controlled-release levodopa products?

No. The claims require specific patient-selection, dosing, formulation, and outcome limitations. A controlled-release levodopa product lacking the claimed layered multiparticulate structure may fall outside the claims.

Can a generic avoid the patent by using a different capsule strength?

Possibly, but not automatically. Claims 1 and 2 include multiple strengths and permit combinations of capsules. A different strength must be analyzed against every limitation, including the formulation structure and dose-conversion ratio.

Is the 5% “Off” time limitation easy to avoid?

It may be difficult to establish from a product label alone, but it can become relevant if clinical instructions or product performance establish the claimed reduction. Its proof value depends on the asserted claim and the evidence available in litigation.

Does a mucoadhesive polymer need to be expressly identified in the generic label?

No. Patent infringement generally turns on the product and its intended use, not solely on label wording. Internal formulation records, testing, discovery, and expert analysis may establish whether the product contains the claimed polymer layer.

Can a generic launch before the patent expires?

It can attempt an at-risk launch after submitting the required ANDA certification and addressing any litigation or stay. Commercial launch timing depends on Paragraph IV notices, suit filing, court orders, settlements, and FDA approval status.

References

1. U.S. Food and Drug Administration. (2024). Crexont (carbidopa and levodopa) extended-release capsules: Prescribing information. FDA.
2. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. FDA Orange Book.
3. U.S. Patent and Trademark Office. (2025). U.S. Patent No. 12,201,596. U.S. Department of Commerce.
4. 21 U.S.C. § 355. Abbreviated applications and patent certifications.
5. 35 U.S.C. § 154. Contents and term of patent; provisional rights.
6. U.S. Food and Drug Administration. (2024). Drug approval package: Crexont. FDA.

Drugs Protected by US Patent 12,201,596

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						TREATMENT OF POST-ENCEPHALITIC PARKINSONISM
Impax	CREXONT	carbidopa; levodopa	CAPSULE, EXTENDED RELEASE;ORAL	217186-001	Aug 7, 2024		RX	Yes	No						TREATMENT OF PARKINSONISM THAT MAY FOLLOW CARBON MONOXIDE INTOXICATION
Impax	CREXONT	carbidopa; levodopa	CAPSULE, EXTENDED RELEASE;ORAL	217186-001	Aug 7, 2024		RX	Yes	No						TREATMENT OF PARKINSONISM THAT MAY FOLLOW MANGANESE INTOXICATION
Impax	CREXONT	carbidopa; levodopa	CAPSULE, EXTENDED RELEASE;ORAL	217186-002	Aug 7, 2024		RX	Yes	No						TREATMENT OF POST-ENCEPHALITIC PARKINSONISM
Impax	CREXONT	carbidopa; levodopa	CAPSULE, EXTENDED RELEASE;ORAL	217186-002	Aug 7, 2024		RX	Yes	No						TREATMENT OF PARKINSONISM THAT MAY FOLLOW CARBON MONOXIDE INTOXICATION
Impax	CREXONT	carbidopa; levodopa	CAPSULE, EXTENDED RELEASE;ORAL	217186-002	Aug 7, 2024		RX	Yes	No						TREATMENT OF PARKINSONISM THAT MAY FOLLOW MANGANESE INTOXICATION

International Family Members for US Patent 12,201,596

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Canada	3196650
China	116801869
Colombia	2023009085
European Patent Office	4267113
Japan	2024501235
South Korea	20230124622