Details for Patent: 8,828,427

Which drugs does patent 8,828,427 protect, and when does it expire?

Patent 8,828,427 protects POMALYST and is included in one NDA.

Protection for POMALYST has been extended six months for pediatric studies, as indicated by the *PED designation in the table below.

This patent has fifty-three patent family members in thirty-three countries.

Summary for Patent: 8,828,427

Title:	Formulations of 4-amino-2-(2,6-dioxopiperidine-3-yl)isoindoline-1,3-dione
Abstract:	Pharmaceutical compositions and single unit dosage forms of 4-amino-2-(2,6-dioxopiperidine-3-yl)isoindoline-1,3-dione, or a pharmaceutically acceptable stereoisomer, prodrug, salt, solvate, hydrate, or clathrate, are provided herein. Also provided are methods of treating, managing, or preventing various disorders, such as cancer or an inflammatory disease.
Inventor(s):	Anthony TUTINO, Michael T. Kelly
Assignee:	Celgene Corp
Application Number:	US12/783,390
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,828,427
Patent Claim Types: see list of patent claims	Composition; Dosage form;

United States Patent 8,828,427: Pomalidomide Formulation Scope, Expiration, and Patent Landscape

US Patent No. 8,828,427 protects narrowly defined pomalidomide capsule formulations containing pregelatinized starch, sodium stearyl fumarate, and spray-dried mannitol. The patent does not broadly protect pomalidomide, its anticancer uses, or every pomalidomide capsule. Its principal coverage is directed to specific capsule fill weights, pomalidomide strengths, excipient quantities, and capsule sizes.

The patent is assigned to Celgene Corporation, now part of Bristol Myers Squibb. Its formulation claims are relevant to Pomalyst capsules and may create an Orange Book and Paragraph IV barrier for generic products that copy the claimed composition.

What does US Patent 8,828,427 protect?

US 8,828,427 protects oral pomalidomide capsule dosage forms with six claimed strength-and-weight combinations:

Claim	Pomalidomide amount	Total composition weight	Pregelatinized starch	Sodium stearyl fumarate	Capsule limitation
1	0.5 mg	62.5 mg	35 mg	0.16 mg	None
3	1 mg	125 mg	70 mg	0.32 mg	None
5	2 mg	250 mg	140 mg	0.64 mg	None
7	3 mg	180 mg	100.8 mg	0.45 mg	None
9	4 mg	240 mg	134.4 mg	0.60 mg	None
11	5 mg	300 mg	168 mg	0.75 mg	None

In each independent claim, spray-dried mannitol is present in a quantity sufficient to bring the composition to the specified total weight. The claims use “comprises,” which generally makes them open-ended as to additional components, subject to the total-weight and specified-quantity limitations.

The dependent claims add capsule-size requirements:

• Claims 2 and 4 require a size 4 or larger capsule.
• Claims 6, 8, and 10 require a size 2 or larger capsule.
• Claim 12 requires a size 1 or larger capsule.

The patent therefore protects both the composition and, in dependent claims, a composition administered in a capsule meeting a minimum capsule size.

How are the claimed formulations constructed?

The claims divide into two formulation patterns.

Lower-strength formulations

The 0.5 mg, 1 mg, and 2 mg formulations contain pregelatinized starch at 70 mg per milligram of pomalidomide:

Strength	Starch-to-pomalidomide ratio	Sodium stearyl fumarate as percentage of total weight
0.5 mg	70:1	0.256%
1 mg	70:1	0.256%
2 mg	70:1	0.256%

These three formulations also use a total composition weight equal to 125 times the pomalidomide strength in milligrams.

Higher-strength formulations

The 3 mg, 4 mg, and 5 mg formulations contain 33.6 mg of pregelatinized starch per milligram of pomalidomide:

Strength	Starch-to-pomalidomide ratio	Sodium stearyl fumarate as percentage of total weight
3 mg	33.6:1	0.250%
4 mg	33.6:1	0.250%
5 mg	33.6:1	0.250%

The claimed 3 mg formulation weighs 180 mg, the 4 mg formulation weighs 240 mg, and the 5 mg formulation weighs 300 mg.

The exact quantities matter. A formulation containing the same excipients but a materially different fill weight, starch amount, lubricant amount, or pomalidomide strength may avoid literal infringement, although it could still raise an infringement argument under the doctrine of equivalents.

What is the claim scope of the “comprises” language?

The independent claims require, at minimum:

1. A capsule oral dosage form.
2. Pomalidomide, or a pharmaceutically acceptable salt or solvate.
3. A specified amount of pomalidomide calculated as 100% pure pomalidomide.
4. A fixed amount of pregelatinized starch.
5. A fixed amount of sodium stearyl fumarate.
6. Spray-dried mannitol sufficient to achieve the stated total composition weight.

“Comprises” generally permits additional excipients. It does not permit omission of a required listed component. A generic formulation containing microcrystalline cellulose instead of spray-dried mannitol would face a stronger noninfringement position because spray-dried mannitol is an express claim limitation.

The “100% pure” language is important. It expresses the quantity of active ingredient on a potency-adjusted basis. A manufacturer using pomalidomide with less than 100% assay would likely need to include a greater physical mass of drug substance to provide the claimed amount of pure pomalidomide.

Do the claims cover Pomalyst capsules?

The claims are closely aligned with the formulation architecture of Pomalyst, the branded pomalidomide product marketed by Celgene and Bristol Myers Squibb.

Pomalyst received FDA approval on February 8, 2013, for multiple myeloma after at least two prior therapies, including lenalidomide and bortezomib, followed by disease progression on the last therapy. The FDA-approved capsule strengths are 1 mg, 2 mg, 3 mg, and 4 mg. The approved label identifies pomalidomide and inactive ingredients that include pregelatinized starch, mannitol, and sodium stearyl fumarate.[1]

The 0.5 mg and 5 mg claims are broader than the currently marketed standard Pomalyst strengths. They can still be commercially relevant because a claim is assessed against the accused product, not only against the marketed dosage strengths.

What patents protect pomalidomide products besides US 8,828,427?

Pomalidomide products have been protected by several patent categories.

Active pharmaceutical ingredient patents

Earlier Celgene patents cover substituted isoindolinone compounds, including pomalidomide and related immunomodulatory compounds. These patents address the chemical entity and may expire earlier than the formulation patent.

Formulation patents

US 8,828,427 is a formulation patent. Its value comes from the precise combination of:

• Pomalidomide strength.
• Capsule fill weight.
• Pregelatinized starch quantity.
• Sodium stearyl fumarate quantity.
• Spray-dried mannitol as the balance.
• Capsule size in dependent claims.

Formulation patents can remain relevant after composition-of-matter patents expire if they are listed for the approved product and are not invalidated or otherwise removed.

Method-of-use patents

Separate patents and regulatory exclusivities may cover the use of pomalidomide in multiple myeloma and other hematologic malignancies. US 8,828,427 does not claim a treatment method. A product can therefore avoid this patent only by avoiding the claimed dosage form; it cannot infringe the patent merely because a physician uses pomalidomide to treat multiple myeloma.

Manufacturing and process patents

Manufacturing patents may cover pomalidomide intermediates, purification, particle-size control, crystallization, or formulation processing. US 8,828,427 does not claim a manufacturing process. It is a product claim directed to the capsule composition.

When does US Patent 8,828,427 expire?

The patent has an earliest claimed priority date of May 6, 2011. Its ordinary patent term is calculated as 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment, terminal disclaimers, and any applicable statutory corrections.[2]

On the public patent record, the expected base-term expiration is in 2031, generally calculated from the 2011 priority chain. The precise enforceable expiration date should be taken from the USPTO patent-term data and the Orange Book listing because patent-term adjustment can change the date.[3]

The patent issued on September 9, 2014. Issue date does not control expiration for a modern utility patent. The controlling term is generally tied to the relevant application filing date, not the date of issuance.

Event	Date
Earliest claimed priority	May 6, 2011
Patent issued	September 9, 2014
Expected base-term period	2031
FDA approval of Pomalyst	February 8, 2013
Orphan-drug exclusivity period	Approximately through February 2020
New-chemical-entity exclusivity period	Approximately through February 2018

Patent expiration and FDA exclusivity are separate. FDA exclusivity limits approval timing. Patent rights can continue after regulatory exclusivity ends.

What is the Orange Book status of US 8,828,427?

US 8,828,427 has been associated with the Pomalyst product patent estate and is relevant to FDA-listed patent analysis for pomalidomide capsules. The Orange Book is the controlling source for whether a patent is currently listed against a specific NDA, the listed expiration date, and any use code.[4]

A listed formulation patent can delay approval of an ANDA through the Hatch-Waxman framework. For a Paragraph IV certification, the NDA holder may have 45 days to file an infringement action. A timely action generally triggers a 30-month stay of FDA approval, subject to court decisions, settlement, patent expiration, or other statutory events.[5]

The commercial relevance of US 8,828,427 depends on four questions:

1. Whether it remains listed for the relevant Pomalyst NDA.
2. Whether the proposed generic uses the claimed excipient and fill-weight structure.
3. Whether the generic applicant filed a Paragraph IV certification.
4. Whether the patent has been invalidated, disclaimed, delisted, or narrowed in litigation.

Which generic companies are challenging pomalidomide patents?

Pomalidomide generic competition has involved ANDA applicants seeking approval for capsules corresponding to Pomalyst. Publicly reported challenges have focused on Celgene’s broader pomalidomide patent portfolio, including composition, formulation, and use patents.

The main litigation risk is not limited to US 8,828,427. A generic applicant may challenge several Orange Book patents in one ANDA, while the NDA holder may assert a subset of them. A settlement may grant a future launch date without producing a public merits decision on validity or infringement.

The absence of a final reported decision against US 8,828,427 should not be interpreted as a finding that the patent is weak. A settlement, nonassertion agreement, design-around, or lack of a directly matching ANDA formulation can prevent a court from reaching the merits.

How strong is the patent estate for US 8,828,427?

The patent has meaningful infringement leverage where a generic copies the commercial formulation. Its strongest features are the combination of exact numerical limitations and the inclusion of common capsule strengths.

Strengths

• The 1 mg, 2 mg, 3 mg, and 4 mg claims map onto commercially relevant Pomalyst strengths.
• The excipients are specified by identity, not merely by function.
• Total composition weight creates a second quantitative limitation.
• The claims cover salts and solvates, not only a single pomalidomide solid form.
• Dependent claims add capsule-size limitations that may correspond to commercial manufacturing configurations.

Vulnerabilities

• The claims are narrow and may be designed around.
• Exact numerical limitations create potential noninfringement positions.
• Prior-art formulation disclosures may challenge novelty or obviousness.
• The patent does not cover pomalidomide API by itself.
• It does not cover every capsule dosage form or every excipient system.
• A generic may use different starch, lubricant, filler, capsule weight, or release design.

The principal invalidity arguments would likely involve anticipation or obviousness based on earlier pomalidomide formulations, conventional capsule excipient systems, and routine dose proportionality. The patent holder’s counterargument would focus on the particular combination of excipient levels, capsule fill weights, potency-adjusted active amounts, and any formulation-performance data in the specification.

What generic launch scenarios exist?

Scenario 1: Exact formulation launch after patent expiry

A generic uses the same or substantially matching quantities and waits until the relevant patent expires. This is the lowest litigation risk but produces the latest entry.

Scenario 2: Paragraph IV challenge

The applicant certifies that the patent is invalid, unenforceable, or not infringed. The NDA holder may sue within 45 days, producing the statutory approval stay. Commercial entry depends on the litigation result or settlement terms.

Scenario 3: Formulation design-around

The generic changes one or more claim-critical variables, such as:

• Replacing spray-dried mannitol.
• Using a different lubricant.
• Altering the capsule fill weight.
• Changing pregelatinized starch quantity.
• Using a different capsule size where the dependent claim applies.
• Selecting a noncapsule oral dosage form.

A design-around may avoid literal infringement but must be evaluated against the doctrine of equivalents and other patents in the Pomalyst estate.

Scenario 4: Authorized generic or settlement entry

Celgene or Bristol Myers Squibb may authorize or license a generic entrant, or settle litigation with a defined launch date. The economic value of such an agreement depends on launch timing, supply rights, volume restrictions, and whether the entrant is an authorized generic or an independent ANDA product.

How does US 8,828,427 compare with the broader pomalidomide estate?

Patent category	Typical subject matter	Relevance to generic capsules
Composition-of-matter	Pomalidomide chemical structure	High before expiration; usually product-wide
Formulation	Excipient composition and capsule weight	High for copycat formulations
Method of use	Multiple myeloma and other indications	Depends on labeling and skinny-label strategy
Manufacturing	API synthesis, purification, particle properties	Relevant to supply chain and CMC design
Regulatory exclusivity	Orphan and NCE exclusivity	Controls FDA approval timing, not patent term
US 8,828,427	Specific pomalidomide capsule compositions	High where commercial formulation is replicated

Does US 8,828,427 create biosimilar risk?

No. Pomalidomide is a small-molecule drug, not a biologic. The relevant competitors are ANDA-based generic applicants, not biosimilar applicants under the Public Health Service Act.

The applicable competitive pathway is the Hatch-Waxman abbreviated new drug application process. Generic applicants must demonstrate pharmaceutical equivalence and bioequivalence, while addressing listed patents through Paragraph I, II, III, or IV certifications.

What geographic coverage does the patent provide?

US 8,828,427 provides rights only in the United States. It does not directly block manufacture, sale, or use outside the United States.

Related foreign patent applications may exist in jurisdictions including Europe, Canada, Japan, and other markets. Their enforceability depends on national prosecution, grant, maintenance, claim scope, supplemental protection certificates, and local litigation. A US expiration date cannot be applied automatically to foreign counterparts.

For global licensing or supply decisions, the critical distinction is between:

• US capsule formulation rights.
• Foreign formulation patents.
• API manufacturing patents.
• Regulatory exclusivities.
• Patent-term extensions or supplementary protection certificates.

Key Takeaways

• US 8,828,427 is a narrow formulation patent, not a broad pomalidomide compound patent.
• Its independent claims cover six exact capsule compositions ranging from 0.5 mg to 5 mg of pomalidomide.
• The 1 mg, 2 mg, 3 mg, and 4 mg strengths are the most commercially relevant to Pomalyst.
• The patent requires pregelatinized starch, sodium stearyl fumarate, and spray-dried mannitol in specified quantitative relationships.
• The expected base-term expiration is in 2031, subject to USPTO patent-term adjustment and Orange Book confirmation.
• The patent is relevant to ANDA Paragraph IV risk and generic formulation design-arounds.
• It does not create biosimilar risk because pomalidomide is a small molecule.
• The primary vulnerabilities are narrow claim scope, quantitative design-around options, and prior-art obviousness arguments.
• The patent must be analyzed with Celgene’s composition, method-of-use, manufacturing, and other formulation patents rather than in isolation.

FAQs

Can a generic use pomalidomide with different excipients?

Yes, potentially. A formulation that omits spray-dried mannitol, pregelatinized starch, or sodium stearyl fumarate may avoid literal infringement of US 8,828,427, although other patents and the doctrine of equivalents must be assessed.

Does the patent cover Pomalyst tablets?

No. The claims require an oral dosage form in the form of a capsule. A tablet would not literally satisfy that limitation.

Does US 8,828,427 cover a 4 mg pomalidomide capsule?

Yes, claim 9 covers a 4 mg capsule composition with a 240 mg total composition weight, 134.4 mg of pregelatinized starch, 0.6 mg of sodium stearyl fumarate, and spray-dried mannitol as the balance.

Can a generic avoid the patent by changing only the capsule shell?

Not necessarily. The claims focus primarily on the dosage-form composition and capsule form. Changing the shell may not avoid infringement if the accused product still contains the claimed fill composition and satisfies the capsule limitations.

Is a pomalidomide salt covered by the patent?

Yes. The claims expressly include pomalidomide, pharmaceutically acceptable salts, and solvates, provided the dosage form satisfies the remaining composition and weight limitations.

References

1. U.S. Food and Drug Administration. (2013). Pomalyst (pomalidomide) prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204026s000lbl.pdf

2. United States Patent and Trademark Office. (2024). Patent term adjustment. https://www.uspto.gov/patents/laws/adjustment

3. United States Patent and Trademark Office. (2014). U.S. Patent No. 8,828,427, Pomalidomide formulations. https://patents.google.com/patent/US8828427B2/en

4. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, Orange Book. https://www.accessdata.fda.gov/scripts/cder/ob/index.cfm

5. U.S. Food and Drug Administration. (2024). Abbreviated new drug application approvals and patent certifications. https://www.fda.gov/drugs/abbreviated-new-drug-application-anda/anda-submissions-content-and-format/drug-master-files-guidance-and-related-information

Drugs Protected by US Patent 8,828,427

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Bristol	POMALYST	pomalidomide	CAPSULE;ORAL	204026-001	Feb 8, 2013	AB	RX	Yes	No					Y
Bristol	POMALYST	pomalidomide	CAPSULE;ORAL	204026-002	Feb 8, 2013	AB	RX	Yes	No					Y
Bristol	POMALYST	pomalidomide	CAPSULE;ORAL	204026-003	Feb 8, 2013	AB	RX	Yes	No					Y
Bristol	POMALYST	pomalidomide	CAPSULE;ORAL	204026-004	Feb 8, 2013	AB	RX	Yes	Yes					Y

International Family Members for US Patent 8,828,427

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2010249615
Brazil	PI1007855
Canada	2752550
Chile	2011001969
China	102333525
China	105640918
China	106176662