Details for Patent: 8,168,218

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Which drugs does patent 8,168,218 protect, and when does it expire?

Patent 8,168,218 protects RAYOS and is included in one NDA.

This patent has twenty-three patent family members in nineteen countries.

Summary for Patent: 8,168,218

Title:	Delayed release tablet with defined core geometry
Abstract:	A press-coated tablet comprising a core containing an drug substance, and a coating, the core being disposed within the coating such that the coating has a first thickness about an axis A-B and a thickness about an orthogonal axis X-Y, such that the coating about the axis X-Y is thicker than the coating about the axis A-B, and is adapted to provide a lag time of between about 2 to 6 hours during which substantially no drug substance is released.
Inventor(s):	Guy Vergnault, Pascal Grenier, Christophe Dragan
Assignee:	Jagotec AG
Application Number:	US10/554,538
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,168,218
Patent Claim Types: see list of patent claims	Use; Formulation; Device; Dosage form;

US Patent 8,168,218: Claim Scope, Patent Landscape, and Generic Entry Risk for Delayed-Release Prednisone

US Patent 8,168,218 protects a highly specific press-coated prednisone tablet designed to release 5 mg of prednisone after a two-to-six-hour lag period with limited food effect. The broadest claim is narrow because it requires a defined core composition, a defined coating composition, anisotropic coating structure, a punch-direction limitation, and delayed-release performance. Claims 2 through 9 add pharmacokinetic, packaging, therapeutic-use, and manufacturing limitations.

The patent is more relevant to a delayed-release prednisone product than to conventional immediate-release prednisone tablets. A generic product that uses a different delayed-release architecture, a different excipient system, or a different release mechanism may avoid literal infringement, although the doctrine of equivalents and regulatory certification remain important.

What does US Patent 8,168,218 cover?

US Patent 8,168,218 covers a press-coated tablet containing 5 mg of prednisone in a rapidly disintegrating or otherwise defined core surrounded by a structurally asymmetric coating. The coating is intended to rupture after approximately two to six hours in an aqueous environment.

The principal technical concept is directional control of water penetration and coating failure:

• The coating is thicker around the X-Y axis.
• The coating is thinner around the orthogonal A-B axis.
• The A-B axis corresponds to the direction of punch movement during press coating.
• The coating around X-Y is relatively less dense.
• The X-Y coating is more permeable to aqueous media.
• The tablet releases prednisone after a delayed lag period.

The claim combines physical structure with functional performance. A competing product would need to be assessed against both the tablet’s composition and its release behavior.

What are the independent claims in US 8,168,218?

Claims 1 and 9 are the principal independent claims.

Claim	Subject matter	Practical significance
1	Press-coated tablet with 5 mg prednisone, specified core and coating composition, asymmetric geometry, density and permeability limitations, and two-to-six-hour release	Primary product claim
9	Method of forming coating granulate, forming core granulate, and press coating the coating material around the core	Manufacturing-process claim

Claim 1 is a product claim. It requires the accused tablet itself to contain the claimed structure and composition.

Claim 9 is a process claim. It is directed to the manufacturing sequence rather than only to the finished dosage form. A manufacturer could potentially avoid claim 9 by using a different manufacturing process even if the finished tablet remains close to claim 1. Conversely, practicing the claimed process could create infringement exposure even if the manufacturer does not market the manufacturing method.

What formulation is protected by US 8,168,218?

The claim recites a 5 mg prednisone core with the following composition:

Core ingredient	Percentage by weight
Prednisone	8.33%
Lactose monohydrate	64.47%
Povidone	6.67%
Croscarmellose sodium	18.33%
Red ferric oxide	0.50%
Vegetable-origin magnesium stearate	1.00%
Colloidal silicon dioxide	0.50%
Total	100.00%

The coating is recited as follows:

Coating ingredient	Percentage by weight
Dibasic calcium phosphate dihydrate	50.00%
Glyceryl behenate	40.00%
Povidone	8.40%
Yellow ferric oxide	0.10%
Vegetable-origin magnesium stearate	1.00%
Colloidal silicon dioxide	0.50%
Total	100.00%

The formulation is therefore not protected merely because it contains prednisone or because it is delayed release. The recited excipient system is central to claim 1. The core contains lactose, povidone, croscarmellose sodium, red ferric oxide, magnesium stearate, and colloidal silicon dioxide. The coating contains dibasic calcium phosphate, glyceryl behenate, povidone, yellow ferric oxide, magnesium stearate, and colloidal silicon dioxide.

The exact percentages create potential design-around opportunities. A competing product that changes the coating matrix, removes glyceryl behenate, substitutes a different filler, or uses a non-press-coated membrane may avoid literal infringement of the composition limitations. The legal outcome would depend on claim construction, prosecution history, and whether the substituted materials perform substantially the same function in substantially the same way.

How does the press-coated geometry limit claim 1?

The geometry limitation is one of the most important constraints in the patent.

Claim 1 requires:

1. A coating around the core.
2. A coating thickness about X-Y that is greater than the coating thickness about A-B.
3. A-B to be the axis of punch movement.
4. Lower density around X-Y than around A-B.
5. Greater water permissiveness around X-Y.
6. Rupture after approximately two to six hours.

This language appears to target the density gradients generated during press coating. Compression forces applied through the punch may produce a denser region in the punch direction and a less dense region in another direction. The claim uses that physical difference to control water ingress and delayed rupture.

A design-around analysis should measure:

• Coating thickness at the relevant axes.
• Tablet orientation relative to punch travel.
• Local porosity and density.
• Water uptake by region.
• Mechanical strength by direction.
• Rupture location and timing.
• Whether the coating is formed by press coating or another process.

The claim does not appear to cover every tablet with a thick coating and a delayed release profile. It requires a particular relationship between thickness, density, permeability, and punch direction.

What dissolution profile does claim 3 require?

Claim 3 narrows the invention to a specified in vitro dissolution result:

• USP Apparatus 2.
• Stirring rate of 100 rpm.
• 500 mL purified water.
• Median lag time of approximately four hours.
• At least 80% drug release after 4.5 hours.
• Approximately 100% release after five hours.

This creates a potentially useful infringement and invalidity issue. The dissolution limitation is measurable, but the terms "about," "median lag time," and "about 100%" may require construction.

For infringement, testing should use the specified apparatus, volume, medium, and agitation. Testing under a different medium or with a different apparatus may not establish whether the claim 3 limitation is met. For validity, the same profile could be relevant to anticipation or obviousness only if a single prior-art reference discloses the complete claimed combination or renders it obvious under applicable patent law.

Claim 3 does not necessarily require the product to release exactly 80% at 4.5 hours and exactly 100% at five hours. The claim uses approximate language, but the boundaries would depend on the specification and prosecution history.

What food-effect and pharmacokinetic limitations are protected?

Claims 4 through 6 add human pharmacokinetic requirements.

Claim	Limitation
4	Fed/fasted Tmax variability differs by less than plus or minus 20%
5	Single-dose fed/fasted Cmax ratio is 0.7 to 1.43
6	Single-dose fed/fasted AUC ratio is 0.8 to 1.25

These claims target administration with or without food. They are narrower than claim 1 because they require clinical or pharmacokinetic characteristics in addition to the tablet structure.

A generic applicant may face practical difficulties with these claims because the relevant information may not be apparent from the product label alone. The claims may require bioavailability or food-effect testing. A product can have the same ingredients but fail to satisfy the claimed fed/fasted ratios. The reverse is also possible: a product with a different composition could meet similar pharmacokinetic results, although it would still need to satisfy all limitations of claim 1 because claims 4 through 6 depend on claim 1.

Does claim 7 protect a package or label?

Yes. Claim 7 covers a pharmaceutical package containing the claimed tablet together with labeling or instructions stating that the tablet may be taken with or without food.

This is a combination claim requiring:

• The patented tablet.
• A package.
• Labeling or instructions.
• The with-or-without-food administration instruction.

The claim may create exposure for a commercial package even if the tablet is manufactured by a third party. Its scope depends on whether the packaged tablet satisfies claim 1.

What diseases and indications are covered by claim 8?

Claim 8 covers methods of treating:

• Arthritic pain.
• Allergies.
• Asthma.
• Crohn's disease.
• Ulcerative colitis.
• Irritable bowel syndrome.
• Inflammatory bowel disease.

The method requires administering the claimed tablet to a patient in need of treatment. This is a method-of-use claim, not a general prednisone indication claim. It is limited by the tablet requirements incorporated from claim 1.

The presence of broad disease categories does not remove the formulation limitations. A product used to treat asthma, for example, would still need to be the claimed press-coated tablet to fall within claim 8.

What does claim 9 protect about manufacturing?

Claim 9 covers a three-step manufacturing method:

1. Forming a first granulate-containing coating material.
2. Forming a core containing a second granulate-containing core material.
3. Press coating the first material around the core.

The method claim is commercially significant because it reaches process execution rather than only the marketed product. It may be relevant in discovery involving batch records, manufacturing instructions, equipment settings, compression force, granulation records, and process validation documents.

A process using film coating, fluid-bed coating, layered compression, osmotic technology, or a multiparticulate capsule may avoid the express press-coating limitation. A process using press coating but different granulation steps could still require analysis under claim construction and the doctrine of equivalents.

How strong is the patent estate based on the issued claims?

The issued claims appear narrow but technically integrated.

Strength factor	Assessment
Product specificity	Narrow because of the exact core and coating composition
Structural specificity	Strong limitation from directional thickness, density, permeability, and punch orientation
Functional limitations	Potentially valuable but may create testing and claim-construction disputes
Manufacturing coverage	Separate process protection through claim 9
Food-effect protection	Additional commercial protection through claims 4-7
Design-around potential	Meaningful because the formulation and manufacturing architecture are detailed
Generic substitution risk	Lower for immediate-release prednisone; higher for closely matching delayed-release tablets
Invalidity exposure	Depends on prior art addressing press-coated delayed release, asymmetric density, and food-independent prednisone delivery

The claims are stronger against a close copy of the claimed delayed-release architecture than against alternative modified-release technologies.

What is the Orange Book status of US 8,168,218?

A patent number alone does not establish current Orange Book listing, delisting, pediatric exclusivity, patent-term adjustment, or the status of any associated abbreviated new drug application certification. Those issues are regulatory-record questions rather than claim-scope questions.

For an Orange Book analysis, the relevant items are:

• Whether the patent is listed for an approved prednisone delayed-release product.
• Whether it is identified as a formulation, drug-substance, or method-of-use patent.
• Whether the listing remains active.
• Whether any Paragraph IV certification has been filed.
• Whether a 30-month stay has been triggered.
• Whether any settlement or consent order affects generic approval timing.

FDA regulations require listed patents to correspond to approved drug product and use information under the applicable listing rules.[2] The existence of an issued patent does not itself establish that an ANDA applicant must certify to it.

When does US Patent 8,168,218 lose exclusivity?

The patent’s enforceable expiration date cannot be determined from the claims supplied. The relevant date depends on the earliest effective nonprovisional filing date, terminal disclaimers, patent-term adjustment, patent-term extension, and any disclaimer or expiration event recorded for the patent.

For a US utility patent, the basic term is generally 20 years from the earliest effective nonprovisional filing date, subject to statutory adjustments.[3] Patent expiration is different from FDA regulatory exclusivity. A product can lose patent protection while retaining regulatory exclusivity, or face patent expiry after regulatory exclusivity has ended.

A commercial freedom-to-operate review should confirm:

• Patent term calculation.
• Patent-term adjustment.
• Terminal disclaimer status.
• Assignment and ownership records.
• Related continuation or divisional applications.
• Orange Book listing and delisting history.
• Any reexamination, reissue, or post-grant proceeding.
• Any litigation or settlement affecting launch timing.

Which companies are likely to challenge this patent?

The most likely challengers would be manufacturers seeking approval for a delayed-release prednisone product that competes with the patented formulation. Conventional generic prednisone manufacturers face less direct exposure if their products are immediate release and do not reproduce the claimed press-coated architecture.

Potential challenge routes include:

• Paragraph IV certification against an Orange Book-listed patent.
• Declaratory-judgment litigation.
• ANDA litigation under the Hatch-Waxman framework.
• Non-infringement based on a different coating process or composition.
• Invalidity based on anticipation or obviousness.
• Regulatory development of a non-infringing modified-release product.

Biosimilar litigation is not relevant to prednisone because prednisone is a small-molecule active ingredient, not a biologic subject to the biosimilar pathway under the Public Health Service Act. The relevant competitive pathway is an ANDA or, depending on the product and regulatory strategy, another small-molecule approval route.

What generic launch scenarios exist?

Scenario	Likely result
Immediate-release prednisone tablet	Usually outside the principal delayed-release claim architecture
Delayed-release tablet with the same formula and press coating	High infringement risk
Delayed-release tablet with different coating excipients	Potential design-around, subject to equivalents analysis
Film-coated or enteric-coated prednisone	Potentially outside claim 1 if no press-coated asymmetric structure
Product with different food-effect profile	May avoid claims 4-6 but not necessarily claim 1
Product using a different manufacturing sequence	Potentially outside claim 9
Product using the same product but a different label	Could affect claim 7 and method-of-use exposure

A Paragraph IV challenge would likely focus on the narrowness of the structural limitations, the meaning of "about," the relationship between axes and punch movement, and prior art concerning press-coated delayed-release dosage forms.

What litigation and settlement issues matter?

The supplied claim text does not establish current litigation, settlement, licensing, or ownership status. Those matters must be evaluated from court dockets, USPTO assignment records, FDA listing data, and publicly filed settlement documents.

The central litigation questions would be:

1. What is the proper construction of X-Y and A-B axes?
2. How is coating thickness measured?
3. What does "relatively less dense" mean quantitatively?
4. What test establishes that a coating is "more permissive" toward water?
5. What is the boundary of "about two to about six hours"?
6. Does the accused product meet the exact formulation percentages?
7. Does a different manufacturing process infringe under equivalents?
8. Was the claimed combination obvious in view of press-coated modified-release tablets and prednisone pharmacokinetics?

Key Takeaways

• US Patent 8,168,218 is directed to delayed-release prednisone, not ordinary immediate-release prednisone.
• Claim 1 requires a 5 mg prednisone core, specified excipient percentages, press coating, asymmetric coating geometry, directional density and permeability differences, and two-to-six-hour delayed release.
• Claims 2 and 3 add in vivo and in vitro release limitations.
• Claims 4 through 6 protect fed/fasted pharmacokinetic performance.
• Claim 7 covers packaging and instructions for administration with or without food.
• Claim 8 covers specified prednisone treatment methods.
• Claim 9 protects a granulation and press-coating manufacturing process.
• The patent is strongest against a close formulation and process copy.
• A product using a different coating technology or materially different excipient system may have a viable design-around position.
• Prednisone does not create biosimilar risk; generic risk is evaluated primarily through the ANDA and Paragraph IV framework.
• Patent expiration, Orange Book listing, litigation, settlements, licensing, and current ownership cannot be established from the claim text alone.

FAQs

Does US Patent 8,168,218 cover all 5 mg prednisone tablets?

No. The claims target a specific delayed-release press-coated tablet with defined formulation, geometry, density, permeability, and release characteristics.

Can an enteric-coated prednisone tablet avoid US 8,168,218?

Potentially. An enteric-coated product may avoid the press-coating and anisotropic-structure limitations, but the final assessment depends on the actual formulation, manufacturing process, and claim construction.

Is the food-effect limitation required for every infringement case?

No. Claims 4 through 6 require the food-effect limitations, but claim 1 does not expressly require the fed/fasted Cmax or AUC ratios. A product may infringe claim 1 without infringing claims 4 through 6.

Does a different prednisone dose avoid the patent?

A different dose may avoid the express "5 mg of prednisone" limitation in claim 1, but the result depends on whether the dosage form otherwise falls within any related claims or patent family members.

Is a patent license required to sell immediate-release generic prednisone?

Not based solely on the issued claims summarized here. The claims are directed to a delayed-release press-coated architecture and related packaging, treatment, and manufacturing features rather than conventional immediate-release prednisone.

References

1. United States Patent and Trademark Office. (2012). U.S. Patent No. 8,168,218, Press-coated pharmaceutical dosage form.
2. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations, Orange Book.
3. United States Code, 35 U.S.C. §§ 154, 271, 271(e), 282.
4. United States Patent and Trademark Office. (n.d.). Manual of Patent Examining Procedure, patent term and claim interpretation provisions.
5. Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 355(j).

Drugs Protected by US Patent 8,168,218

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Horizon	RAYOS	prednisone	TABLET, DELAYED RELEASE;ORAL	202020-003	Jul 26, 2012		DISCN	Yes	No			Y			TREATMENT OF RHEUMATOLOGIC, ALLERGIC, PULMONARY, GASTROINTESTINAL, DERMATOLOGIC DISEASES OR CONDITIONS BY THE USE OF A DELAYED RELEASE 5MG PREDNISONE TABLET

Foreign Priority and PCT Information for Patent: 8,168,218

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
United Kingdom	0309342.4	Apr 24, 2003

PCT Information
PCT Filed	April 23, 2004	PCT Application Number:	PCT/IB2004/001693
PCT Publication Date:	November 04, 2004	PCT Publication Number:	WO2004/093843

International Family Members for US Patent 8,168,218

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	512659
Australia	2004231362
Brazil	PI0409652
Canada	2523158