Details for Patent: 10,098,845

Which drugs does patent 10,098,845 protect, and when does it expire?

Patent 10,098,845 protects CREXONT and is included in one NDA.

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

Summary for Patent: 10,098,845

Title:	Muco-adhesive, controlled release formulations of levodopa and/or esters of levodopa and uses thereof
Abstract:	The invention provides a controlled release oral solid formulation comprising (a) a controlled release component comprising core comprising levodopa and/or an ester of levodopa or salts thereof, wherein the core is coated with a layer of a muco-adhesive polymer and externally coated with a layer of an enteric coated polymer; and (b) a decarboxylase inhibitor component.
Inventor(s):	Ann Hsu, Liang C. Dong, Amy Ding, Suneel Gupta
Assignee:	Impax Laboratories LLC
Application Number:	US15/027,654
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,098,845
Patent Claim Types: see list of patent claims	Use; Formulation; Dosage form;

United States Patent 10,098,845: Levodopa Controlled-Release Formulation Patent Analysis

U.S. Patent No. 10,098,845 covers a multipart oral levodopa dosage form combining an immediate-release component with an enteric-protected, mucoadhesive, controlled-release component. The broadest claim requires both a specific multilayer architecture and a defined fasting-state pharmacokinetic profile. The patent is therefore most relevant to multiparticulate levodopa products using beads, mini-tablets, or granules rather than conventional monolithic sustained-release tablets.

The principal infringement risks are concentrated in four areas: the layered controlled-release particle, the dimethylaminoethyl methacrylate mucoadhesive layer, the immediate-release/controlled-release combination, and the claimed levodopa exposure profile.

What does U.S. Patent 10,098,845 protect?

The patent claims a controlled-release oral solid formulation for levodopa or specified levodopa esters and salts. Claim 1 requires every element below:

Claim element	Required scope
Active ingredient	Levodopa, a levodopa ester, or a salt
Controlled-release unit	Mini-tablet, bead, or granule
Core	Contains the levodopa active
First coating	Rate-controlling polymer
Second coating	Mucoadhesive layer containing a dimethylaminoethyl methacrylate copolymer
Outer coating	Enteric coating polymer
Immediate-release component	Separate levodopa-containing component
Pharmacokinetics	Cmax within six hours, 50% Cmax reached in less than one hour, and levodopa maintained at or above 50% Cmax for at least five hours under fasting conditions

The patent does not merely claim levodopa extended release. It claims a specific dosage-form system intended to combine rapid initial exposure with prolonged plasma maintenance.

The independent claim is a combination claim. A product containing only controlled-release levodopa, without the separate immediate-release component, would not satisfy claim 1. A product using an immediate-release component and sustained-release beads could still avoid claim 1 if its controlled-release particles lack the specified mucoadhesive dimethylaminoethyl methacrylate layer or fail the claimed pharmacokinetic limitations.

How strong is the broadest composition claim?

Claim 1 has meaningful technical breadth but several narrowing limitations.

Its breadth comes from the alternative forms of the controlled-release component: mini-tablets, beads, and granules. It also covers levodopa, levodopa esters, and salts. The immediate-release component is not limited to a particular dosage form in claim 1, although claim 2 narrows it to mini-tablets, beads, or granules.

Its limitations are substantial:

1. The controlled-release unit must have a core and three successive functional layers.
2. The mucoadhesive layer must contain a dimethylaminoethyl methacrylate copolymer.
3. The formulation must include an immediate-release levodopa component.
4. The formulation must meet the specified in vivo plasma profile.
5. The pharmacokinetic profile must be established under fasting conditions.

A generic or competing product that uses hydroxypropyl methylcellulose, ethylcellulose, lipid matrices, or ion-exchange resins without the claimed multilayer structure may have a credible non-infringement position. The risk increases when a product uses coated multiparticulates with a gastric-resistant outer layer and a pH-dependent mucoadhesive polymer.

What formulations are protected by the dependent claims?

The dependent claims create several narrower but commercially relevant claim positions.

Polymer and coating limitations

Claims 5 through 8 specify the coating materials:

Claim	Added limitation
5	Mucoadhesive layer also contains one or more listed polymers, including polycarbophil, carbomer, cellulosics, chitosan, sodium CMC, or alginate
6	Rate-controlling polymer is cellulose acetate or ethylcellulose
7	Rate-controlling polymer includes cellulose acetate and copovidone
8	Enteric coating contains one or more methacrylic acid copolymers

Claim 7 is particularly relevant to formulation design because it identifies a cellulose acetate/copolyvidone combination. Claim 8 captures common enteric systems based on methacrylic acid copolymers, including polymers commonly used for pH-dependent gastrointestinal release.

A product using a different rate-controlling polymer may avoid claims 6 and 7 while remaining exposed to claim 1. A product using a non-methacrylate enteric coating may avoid claim 8 but could still fall within claim 1 if the outer layer qualifies as an enteric coating polymer.

Active ingredient and salt scope

Claims 9 and 10 extend the patent beyond unmodified levodopa. Claim 9 identifies:

• Levodopa ethyl ester
• Levodopa butyl ester
• Levodopa methyl ester

Claim 10 identifies octanoate, myristate, succinate, succinate dihydrate, fumarate, and fumarate dihydrate salts.

These claims may have practical value if a product uses a prodrug or alternative salt to alter solubility, stability, absorption, or dose loading. The claims do not appear limited to a particular levodopa-to-ester ratio or a specific salt concentration based on the supplied text.

Does the patent claim the pharmacokinetic performance of the product?

Yes. The pharmacokinetic profile is a material limitation of claim 1.

The required fasting-state profile is:

• Cmax within six hours;
• time to reach 50% of Cmax below one hour; and
• plasma levodopa maintained at or above 50% of Cmax for at least five hours.

Claims 13 through 16 extend the maintenance period to at least 5.5, 6.0, 6.5, and 7.0 hours. These claims are nested limitations. A formulation meeting the seven-hour threshold would generally satisfy the lower duration thresholds as well, assuming the other limitations are present.

The pharmacokinetic language creates both enforcement value and litigation risk. The patentee would need to show that the accused product produces the claimed profile under the specified testing conditions. The accused party could challenge:

• the fasting protocol;
• the definition and calculation of Cmax;
• the number and timing of pharmacokinetic samples;
• whether “50% Cmax” is measured against individual-subject or mean Cmax;
• whether the plasma level must remain continuously above the threshold;
• whether the claimed profile is inherent in every batch or only demonstrated in a clinical study.

The claim language appears to describe a product by its performance, but it does not eliminate the need to prove the structural formulation elements.

What dissolution characteristics are protected?

Claims 11 and 12 impose a two-stage dissolution profile:

1. Less than 20%, or less than 10%, release at approximately pH 1.0 during the first two hours.
2. After the dissolution medium changes to approximately pH 7.0, extended release over at least four to eight hours.

The test is specified as a USP I dissolution method at a speed of 75. This limitation is directed to gastric protection followed by prolonged release in a higher-pH environment.

Claim	Acid-stage limitation	Neutral or intestinal-stage limitation
11	Less than 20% release at pH 1.0 for two hours	Extended release for four to eight hours after pH change to approximately 7.0
12	Less than 10% release at pH 1.0 for two hours	Same extended-release framework

These claims are important in product comparisons because two products may have similar clinical pharmacokinetics but materially different dissolution profiles. A product with rapid acid-stage release may avoid claims 11 and 12 while remaining subject to claim 1 if it meets the in vivo profile and structural limitations.

What bead sizes and manufacturing configurations are covered?

Claims 18 through 22 address physical manufacture and dosage-form construction.

Claims 18 through 21 cover beads in the approximate 0.8 to 1.2 mm range or beads classified by mesh retention. The mesh limitations specify beads that pass through a 12-, 14-, or 16-mesh screen but may be retained on an 18-, 24-, or 25-mesh screen.

Claim 22 covers two active-loading arrangements:

• levodopa dispersed throughout the core; or
• levodopa layered on a sugar sphere.

These limitations can matter in an abbreviated regulatory or litigation review because bead size, starter cores, layering equipment, and coating sequence may be discoverable from manufacturing records, batch specifications, and regulatory filings.

The claims do not appear limited to a particular capsule fill weight, capsule shell, dose strength, bead-count range, or manufacturing equipment. Claim 4, however, expressly covers encapsulation in a capsule.

What method-of-use protection does the patent provide?

Claim 17 covers a method of treating Parkinson's disease or primary parkinsonism by administering an effective amount of the formulation of claim 1.

This is narrower than a broad method claim to treating Parkinson's disease with levodopa. It incorporates the limitations of claim 1, including the multilayer controlled-release component, the immediate-release component, and the pharmacokinetic profile.

The method claim may be relevant to induced infringement where a product label instructs administration of a dosage form that meets the formulation limitations. Its commercial significance depends on whether the product labeling directs use for Parkinson's disease or primary parkinsonism and whether the label or clinical materials support the claimed dosing conditions.

How does this patent compare with Rytary, Sinemet CR, and other levodopa products?

The patent is technically differentiated from conventional levodopa products by its multiparticulate architecture and combination release profile.

Product category	Typical delivery approach	Overlap risk with Patent 10,098,845
Immediate-release carbidopa/levodopa	Rapid dissolution and absorption	Low unless combined with covered controlled-release particles
Conventional sustained-release tablets	Matrix or coated-tablet release	Depends on the presence of the claimed multilayer particle and mucoadhesive polymer
Rytary	Extended-release carbidopa/levodopa capsules containing multiparticulates	Potentially relevant at the dosage-form level, but infringement requires the specific claimed polymer layers and PK profile
Duopa or intestinal gel	Continuous intestinal delivery	Low for the oral solid formulation claims
Inbrija	Inhaled levodopa powder	No direct overlap with the oral solid formulation claims
Future oral multiparticulate products	Immediate-release plus controlled-release particles	Higher structural and functional overlap risk

Rytary is the closest commercial comparator because it uses an oral capsule with immediate-release and extended-release components. Similarity at the release-profile level does not establish infringement. The key distinction is whether the competitor's particles include the claimed dimethylaminoethyl methacrylate copolymer mucoadhesive layer between the rate-controlling layer and enteric layer.

What is the Orange Book status of U.S. Patent 10,098,845?

A patent number alone does not establish Orange Book listing status. The FDA Orange Book lists patents submitted for approved drug products, including patents identified by the approved product sponsor under the applicable FDA regulations. A patent covering an unapproved development formulation generally has no Orange Book relevance until tied to an approved product and submitted by the sponsor [2].

The claims supplied are directed to a levodopa oral solid formulation, but they do not identify an approved product, NDA, sponsor, or listed drug. The patent should therefore be analyzed separately from Orange Book-listed patents for Rytary, Sinemet, Crexont, or other carbidopa/levodopa products. An Orange Book listing would matter for regulatory exclusivity, Paragraph IV certification, and the potential 30-month stay under the Hatch-Waxman framework. Patent rights outside the Orange Book can still support infringement litigation but generally do not create the same listed-patent certification pathway.

When does Patent 10,098,845 lose exclusivity?

The patent's enforceable term depends on its earliest effective nonprovisional filing date, patent-term adjustment, terminal disclaimers, and any patent-term extension. The issue date alone does not establish the expiration date.

For a conventional utility patent, the baseline term is generally 20 years from the earliest effective U.S. nonprovisional filing date, subject to statutory adjustments. Patent-term adjustment may extend the term for qualifying USPTO delays, while a terminal disclaimer may shorten it. Patent-term extension under 35 U.S.C. § 156 is generally associated with regulatory review and must be established from the patent and approved product records [3].

The expiration date must therefore be taken from the official USPTO patent record and any applicable terminal disclaimer or patent-term adjustment data. The claims themselves do not provide that date.

Which companies are most likely to challenge the patent?

The most exposed parties would be companies developing:

• generic or reformulated oral carbidopa/levodopa capsules;
• multiparticulate levodopa products;
• levodopa products combining immediate-release and extended-release fractions;
• Parkinson's disease products designed to reduce off-time through prolonged plasma exposure;
• levodopa ester or salt products using coated beads.

Potential challengers would likely focus on claim construction and proof of the functional limitations. The main non-infringement positions would be:

1. no dimethylaminoethyl methacrylate copolymer;
2. no distinct immediate-release component;
3. no enteric outer layer;
4. no qualifying bead, mini-tablet, or granule;
5. failure to meet the fasting-state pharmacokinetic profile;
6. failure to meet the acid-stage dissolution limitation;
7. use of a non-covered levodopa derivative or salt.

Validity challenges could target written description, enablement, obviousness, indefiniteness of the pharmacokinetic limitations, and whether the claimed combination was predictable from prior sustained-release levodopa systems. The presence of multiple polymer layers and performance thresholds gives the patentee a detailed technical position, but it also creates multiple potential attack points.

What manufacturing and intellectual-property barriers does the patent create?

The patent may create practical barriers even where a competitor changes one formulation variable. A design-around may require simultaneous modification of:

• the rate-controlling polymer;
• the mucoadhesive polymer;
• the enteric coating;
• the particle size;
• the active-loading method;
• the ratio of immediate-release to controlled-release material;
• the release profile under acidic and neutral conditions.

A change to one component may preserve the desired pharmacokinetic profile but still leave the product exposed to claim 1. A more robust design-around would avoid the claimed combination of polymer layers and use a different release mechanism, such as a matrix tablet, osmotic system, lipid multiparticulate, ion-exchange resin, or non-mucoadhesive coated particle.

Manufacturing records are likely to be important in any dispute. The claimed structure may be evaluated through coating composition records, in-process controls, particle-size data, dissolution testing, microscopy, spectroscopy, and batch-release specifications.

What is the overall patent strength?

The patent has moderate-to-strong blocking potential against products that copy the claimed multiparticulate design. Its strongest positions are:

• the combination of immediate-release and controlled-release components;
• the three-layer controlled-release particle;
• the mucoadhesive dimethylaminoethyl methacrylate copolymer;
• the fasting-state exposure profile;
• the dependent polymer and dissolution claims.

Its principal weaknesses are claim complexity and proof burden. A competitor may avoid infringement by changing the mucoadhesive polymer, eliminating the enteric layer, using a different release architecture, or demonstrating that the product does not meet the claimed pharmacokinetic threshold. The patent is less threatening to conventional immediate-release products, inhaled levodopa, intestinal gel products, and sustained-release systems that do not use the claimed layered particle.

What patent litigation and Paragraph IV risks should be monitored?

A Paragraph IV challenge would be relevant only if the patent is listed against an approved reference product and a generic applicant files an ANDA with the required certification. The supplied claims do not identify an Orange Book reference product or an ANDA dispute.

For commercial diligence, the relevant monitoring points are:

• USPTO assignment and maintenance records;
• terminal disclaimers and patent-term adjustment;
• FDA Orange Book listings;
• ANDA Paragraph IV notices;
• district court complaints under 21 U.S.C. § 271(e)(2);
• PTAB inter partes review petitions;
• claim construction orders;
• settlement agreements involving generic launch dates;
• licensing or assignment transactions involving the patent owner.

A settlement could establish an authorized generic, a delayed generic entry date, or a license limited by geography, indication, dosage strength, or formulation architecture. No settlement terms should be inferred from the claim text alone.

Key Takeaways

• U.S. Patent 10,098,845 claims a multipart oral levodopa system, not generic sustained-release levodopa.
• Claim 1 requires a controlled-release core with rate-controlling, mucoadhesive, and enteric layers.
• The mucoadhesive layer must contain a dimethylaminoethyl methacrylate copolymer.
• The formulation must also contain a separate immediate-release levodopa component.
• Claim 1 includes fasting-state pharmacokinetic limitations requiring rapid initial exposure and at least five hours above 50% Cmax.
• Claims 11 and 12 add gastric-resistant and pH-shift dissolution requirements.
• Claims 18 through 22 address bead size, mesh classification, and active loading on or within the core.
• Rytary-type multiparticulate products present the closest structural comparison, but commercial similarity does not establish infringement.
• Orange Book relevance depends on an approved product listing and sponsor submission.
• The patent's expiration date cannot be determined from the claims alone and must be taken from the official USPTO term records.
• The strongest design-around strategy is to avoid the claimed multilayer mucoadhesive particle architecture rather than change only the immediate-release fraction.

FAQs

Does Patent 10,098,845 cover carbidopa/levodopa?

Claim 3 expressly permits a decarboxylase inhibitor, which includes carbidopa in an appropriate formulation. The independent claim, however, is directed to levodopa or specified levodopa derivatives and does not require carbidopa.

Can a levodopa matrix tablet infringe Patent 10,098,845?

A matrix tablet would generally face lower risk if it lacks the claimed core, rate-controlling layer, dimethylaminoethyl methacrylate mucoadhesive layer, and enteric coating sequence. The product must still be assessed against every claim limitation.

Are levodopa ester salts independently protected?

Yes. Claims 9 and 10 expressly identify several levodopa esters and salts, including ethyl, butyl, and methyl esters and specified octanoate, myristate, succinate, and fumarate salts.

Does achieving a five-hour levodopa profile alone create infringement?

No. The pharmacokinetic profile is only one part of claim 1. The product must also contain the claimed controlled-release particle structure and separate immediate-release component.

Can a generic applicant file a Paragraph IV certification to this patent?

Only if the patent is listed in the FDA Orange Book for the relevant reference product. The patent number and claim language alone do not establish that it is an Orange Book-listed patent.

References

1. United States Patent and Trademark Office. (2018). U.S. Patent No. 10,098,845, Controlled release oral solid formulation comprising levodopa. Washington, DC: U.S. Department of Commerce.

2. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book. Silver Spring, MD: U.S. Department of Health and Human Services.

3. United States Patent and Trademark Office. (2024). Patent term adjustment and patent term extension. Washington, DC: U.S. Department of Commerce.

Drugs Protected by US Patent 10,098,845

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

International Family Members for US Patent 10,098,845

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2014332024
Australia	2019284060
Australia	2021282393
Canada	2926082
China	105658211
European Patent Office	3054929
European Patent Office	3782614