Details for Patent: 8,835,501

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Which drugs does patent 8,835,501 protect, and when does it expire?

Patent 8,835,501 protects BELEODAQ and is included in one NDA.

This patent has forty-one patent family members in twenty-six countries.

Summary for Patent: 8,835,501

Title:	Pharmaceutical formulations of HDAC inhibitors
Abstract:	This invention pertains to pharmaceutical compositions comprising certain carbamic acid compounds (e.g., which inhibit HDAC (histone deacetylase) activity) (e.g., PXD-101, N hydroxy-3-(3-phenylsulfamoyl-phenyl)-acrylamide)) and one or more additional ingredients selected from cyclodextrin, arginine, and meglumine. The present invention also pertains to the use of such compositions, for example, in the inhibition of HDAC, and in the treatment of conditions mediated by HDAC, cancer, proliferative conditions, psoriasis, etc.
Inventor(s):	Richard J. Bastin, Nicholas J. Hughes
Assignee:	SWK Funding LLC
Application Number:	US11/913,191
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,835,501
Patent Claim Types: see list of patent claims	Composition; Formulation; Compound; Device; Dosage form;

US Patent 8,835,501: Scope, Claims, Expiration, Orange Book Status, and HDAC Inhibitor Patent Landscape

US Patent 8,835,501 protects injectable and solid pharmaceutical formulations of certain histone deacetylase inhibitors, principally belinostat formulations using free arginine or meglumine as an in situ salt former. Its strongest commercial coverage is directed to aqueous parenteral products containing approximately 50 mg/mL belinostat, L-arginine at a defined molar ratio, and water in a vial or ampoule. The patent is formulation-focused rather than a basic compound patent.

What does US Patent 8,835,501 protect?

The patent covers pharmaceutical compositions containing:

1. An HDAC inhibitor within a defined chemical genus or a specifically identified HDAC inhibitor.
2. Free arginine, L-arginine, meglumine, or free meglumine as a basic in situ salt former.
3. A pharmaceutically acceptable carrier or excipient.

The commercial relevance is the use of a basic excipient to improve the solubility and injectable formulation properties of an otherwise poorly water-soluble HDAC inhibitor.

The principal protected product architecture is:

Element	Scope
Active ingredient	HDAC inhibitor within the claimed genus, including the specifically claimed compound
Salt former	Free arginine, L-arginine, meglumine, or free meglumine
Carrier	Pharmaceutically acceptable excipient or carrier
Preferred dosage form	Aqueous liquid
Preferred route	Parenteral, injectable, or infusion administration
Preferred concentration	About 50 mg/mL in the narrow claims
Preferred container	Vial, ampoule, or IV infusion bag

The patent does not broadly claim every formulation of every HDAC inhibitor. A product must satisfy the claimed HDAC inhibitor identity and the required basic salt former.

Which HDAC inhibitor is covered by the narrow claims?

The omitted chemical structures in the supplied text correspond to the specific HDAC inhibitor used in the patent's commercial formulation claims. The relevant product is belinostat, also known as Beleodaq.

Belinostat is a hydroxamic-acid HDAC inhibitor with the chemical name (2E)-N-hydroxy-3-[3-(phenylsulfamoyl)phenyl]acrylamide. Beleodaq is supplied as a sterile lyophilized powder for intravenous infusion and contains belinostat and L-arginine. FDA labeling identifies reconstitution and dilution procedures using sterile water and compatible infusion solutions.[2]

The narrow claim set is materially stronger than the broad genus claim because it eliminates disputes over whether a particular HDAC inhibitor falls within the Markush definition.

How broad is claim 1?

Claim 1 is a composition claim with three principal limitations:

• An HDAC inhibitor.
• At least one specified basic in situ salt former.
• A pharmaceutically acceptable excipient or carrier.

The HDAC inhibitor is defined through a complex Markush structure containing:

• A substituted or unsubstituted carboaryl or heteroaryl group.
• An optional alkylene or alkenylene linker.
• A sulfonamide linkage.
• A second substituted or unsubstituted aryl, heteroaryl, or linked aryl system.
• Pharmaceutically acceptable salts of qualifying compounds.

This genus potentially captures a wide range of sulfonamide-containing HDAC inhibitors. Its practical enforceability depends on whether the accused active ingredient satisfies every structural limitation, including the identity and position of the aryl, heteroaryl, linker, and sulfonamide groups.

The term "consisting essentially of" narrows the composition relative to an open "comprising" claim. It permits additional components that do not materially alter the basic and novel characteristics of the formulation. An accused formulation containing another buffer, stabilizer, tonicity agent, antioxidant, or preservative could still fall within the claim if that ingredient does not materially change the claimed salt-forming and solubilizing system.

What do claims 2 through 9 cover?

Claims 2 through 9 narrow the HDAC inhibitor and salt-former limitations.

Claims	Main limitation
2	Selected compounds from the patent's HDAC inhibitor list
3	A further narrowed HDAC inhibitor selection
4	The specifically identified HDAC inhibitor
5	Meglumine added to the claim 3 formulation
6	Free L-arginine
7	Free meglumine or a pharmaceutically acceptable meglumine salt
8	Arginine-to-HDAC-inhibitor molar ratio of at least 0.5:5
9	Meglumine-to-HDAC-inhibitor molar ratio of at least 0.5:5

The ratio limitations are important because they create measurable infringement criteria. A generic applicant would need to assess the actual molar quantity of arginine or meglumine relative to the HDAC inhibitor, not merely whether the excipient is present.

The wording "at least 0.5 to 5" is structurally awkward and should be construed against the specification and prosecution history. In commercial terms, the narrower dependent claims focus on formulations containing a substantial amount of arginine or meglumine rather than trace excipient levels.

What formulations are protected by claims 10 through 26?

Claims 10 through 26 divide the formulation estate into liquid and solid products.

Liquid and aqueous formulations

Claims 10 and 11 cover liquid and aqueous liquid formulations. Claims 12 and 13 identify specific carriers, including:

• Water for injection.
• Aqueous saline.
• Aqueous glucose.
• Saline for injection or infusion.
• Glucose for injection or infusion.
• Ringer's solution.
• Lactated Ringer's solution.

Claims 14 through 21 specify alternative concentration ranges:

Claims	Concentration range
14	0.1-1,000 mg/mL
15	30-300 mg/mL
16	0.3-3,000 mM
17	100-500 mM
18	0.01-300 mg/mL
19	1.0-10 mg/mL
20	0.01-100 mM
21	3-30 mM

These ranges overlap extensively. The overlapping claims provide fallback positions if a broader concentration claim is invalidated or avoided.

Claims 22 through 24 cover suitability for:

• Parenteral administration.
• Injection.
• Infusion.

Solid formulations

Claims 25 and 26 cover solid formulations, including:

• Powders.
• Granules.
• Tablets.
• Lyophilized or lyophilisate products.

The solid claims are broader in dosage-form terms but are commercially less central to Beleodaq, which is an injectable product.

What do claims 27 through 29 cover?

Claims 27 through 29 extend protection beyond the composition itself.

Claim	Covered article
27	IV infusion bag containing the claimed liquid formulation
28	Vial or ampoule containing the claimed liquid formulation
29	Kit containing the formulation, packaging, and instructions

These claims create potential infringement exposure for finished-product configurations. A generic manufacturer could avoid a particular container claim by changing packaging, but that would not avoid the underlying composition claims if the formulation remains within their scope.

What do claims 30 through 39 protect?

Claims 30 through 39 are the most commercially targeted claims. They focus on an aqueous liquid composition containing the specifically identified HDAC inhibitor, a permitted basic salt former, and water.

The key limitations are:

• Aqueous liquid formulation.
• Approximately 50 mg/mL HDAC inhibitor.
• L-arginine-to-HD inhibitor molar ratio of 0.8 to 4.
• Vial or ampoule presentation.

The practical claim hierarchy is:

1. Claim 30: specific aqueous liquid formulation.
2. Claim 31: approximately 50 mg/mL concentration.
3. Claim 32: L-arginine ratio of 0.8 to 4.
4. Claims 33 and 34: vial or ampoule containing the formulation.
5. Claims 35 through 39: parallel aqueous composition and container claims with water expressly recited.

These claims are likely the principal Orange Book and generic-entry barriers because they map closely onto the marketed injectable product.

When does US Patent 8,835,501 lose exclusivity?

The patent was granted on September 16, 2014. Its nominal patent term is tied to the applicable nonprovisional priority chain and statutory patent-term calculation. The patent is generally treated as having an expiration date in 2029, subject to any patent-term adjustment, terminal disclaimer, or other USPTO term modification.[1]

FDA approval exclusivity for Beleodaq is separate from patent exclusivity. Beleodaq received FDA approval on July 3, 2014, for relapsed or refractory peripheral T-cell lymphoma.[3] The drug's regulatory exclusivity period does not replace the patent and does not determine the patent expiration date.

Exclusivity timeline

Event	Date
US Patent 8,835,501 grant	September 16, 2014
Beleodaq FDA approval	July 3, 2014
Nominal patent-expiration period	2029
Small-molecule generic pathway	ANDA under Hatch-Waxman
Biosimilar pathway	Not applicable

The operative expiration date for litigation and ANDA timing should be taken from the current USPTO patent record and the FDA Orange Book entry.

What is the Orange Book status of US Patent 8,835,501?

US Patent 8,835,501 is associated with the injectable belinostat product Beleodaq and is the type of formulation patent that can be listed in the FDA Orange Book for an approved drug product.[4]

The listing matters because an ANDA applicant referencing Beleodaq must address the listed patent through one of the following certifications:

• Paragraph I: no patent information has been submitted.
• Paragraph II: the patent has expired.
• Paragraph III: the applicant will wait until patent expiration.
• Paragraph IV: the patent is invalid, unenforceable, or will not be infringed.

A Paragraph IV certification can trigger a patent infringement action under 35 U.S.C. § 271(e)(2). A timely action by the NDA holder can create a statutory stay of FDA approval for up to 30 months, subject to the Hatch-Waxman framework.[5]

Which companies are likely to challenge the patent?

The likely challengers are manufacturers developing an ANDA for generic belinostat injection. The relevant competitive group includes established injectable generic manufacturers and specialty oncology suppliers.

Publicly confirmed Paragraph IV activity should be established from FDA ANDA records, court dockets, and Orange Book updates. The patent number alone does not establish that a particular company has filed a Paragraph IV certification or that litigation is pending.

A generic applicant can pursue several design-around strategies:

1. Use a different solubilizer instead of arginine or meglumine.
2. Use a different concentration outside the asserted range.
3. Use a nonaqueous or alternative liquid system.
4. Use a different salt or prodrug of the active ingredient.
5. Use a solid formulation rather than the marketed aqueous product.
6. Alter the arginine-to-bel inostat molar ratio.
7. Challenge the structural scope or validity of the claims.

The first strategy is likely the most commercially significant because the patent expressly identifies arginine and meglumine as required salt formers.

What are the principal validity risks?

Written description and enablement

The broad Markush genus includes many possible aryl, heteroaryl, linker, and sulfonamide combinations. A challenger could argue that the specification does not adequately describe or enable the full genus, particularly if the examples focus on a small number of compounds.

Indefiniteness

Potential claim-construction disputes may concern:

• "Consisting essentially of."
• "Basic in situ salt former."
• "About 50 mg/mL."
• The ratio wording in claims 8 and 9.
• The breadth of the structural Markush language.

Anticipation and obviousness

Prior art relating to HDAC inhibitor formulations, arginine-assisted solubilization, meglumine salts, injectable oncology products, and lyophilized formulations may be relevant. The strongest obviousness argument would combine:

• A known poorly soluble HDAC inhibitor.
• Known use of arginine or meglumine to increase aqueous solubility.
• Known parenteral formulation practices.
• Routine selection of concentration and excipient ratios.

The patent holder's counterargument would focus on unexpected solubility, stability, concentration, or infusion compatibility results.

Double patenting and prosecution history

Any terminal disclaimer, amended claim language, or examiner interpretation of the Markush structure could materially affect enforceability. The prosecution history is particularly important for determining whether the claims were narrowed to belinostat, L-arginine, specific ratios, or aqueous injectable products.

How does this patent compare with belinostat compound patents?

Patent category	Subject matter	Commercial impact
Basic compound patent	Belinostat molecule and related HDAC inhibitors	Protects the active pharmaceutical ingredient
Formulation patent	Arginine or meglumine solubilized compositions	Protects the injectable product architecture
Method-of-use patent	Treatment of cancer or lymphoma	May restrict labeled uses
Manufacturing patent	Synthesis, purification, or solid forms	Can create API supply barriers
Regulatory exclusivity	FDA approval protection	Controls approval timing independently of patent validity

US Patent 8,835,501 is strongest against a generic that copies the marketed formulation. It is less powerful against a generic that uses the same belinostat active ingredient in a materially different formulation.

Are biosimilar challenges relevant?

No. Belinostat is a chemically synthesized small molecule, not a biologic. The relevant competitive pathway is an ANDA, not a biosimilar application under the Biologics Price Competition and Innovation Act.

Biosimilar concepts such as interchangeability, reference-product exclusivity, and the Purple Book do not govern Beleodaq. Generic applicants must address the Orange Book-listed patents and applicable FDA exclusivity through Hatch-Waxman procedures.

What licensing deals affect the patent estate?

TopoTarget developed belinostat and entered into a US commercialization arrangement with Spectrum Pharmaceuticals. Spectrum commercialized Beleodaq in the United States, and the product later became associated with Acrotech Biopharma following Acrotech's acquisition of Spectrum's oncology portfolio.[6]

The commercial license chain matters because patent enforcement authority, Orange Book ownership, NDA ownership, and royalty obligations may reside with different entities. Patent ownership should be confirmed through current USPTO assignment records rather than inferred from the product label alone.

What generic launch scenarios exist?

Scenario 1: Paragraph III filing

The applicant accepts the patent and seeks approval after expiration. This minimizes litigation risk but delays launch.

Scenario 2: Paragraph IV challenge

The applicant alleges invalidity, unenforceability, or noninfringement. Litigation can delay approval and may create a first-filer opportunity if the statutory conditions are met.

Scenario 3: Formulation design-around

The applicant uses belinostat but replaces arginine and meglumine or changes the concentration and dosage form. This approach reduces formulation-patent exposure but requires new pharmaceutical development and FDA comparability work.

Scenario 4: Alternative dosage form

A solid, nonaqueous, or differently packaged product could avoid the narrow aqueous-vial claims. Commercial substitution would depend on demonstrating bioequivalence and clinical usability.

How strong is the patent estate?

The patent estate has moderate-to-strong commercial value for the marketed injectable formulation and weaker value against all belinostat products.

Risk area	Assessment
Copying marketed arginine formulation	High
Copying approximately 50 mg/mL aqueous product	High
Different excipient system	Lower
Different concentration	Dependent on claim construction
Alternative dosage form	Lower
Belinostat API competition	Not independently blocked by this patent
Biosimilar competition	Not applicable
Patent litigation exposure	Primarily ANDA-driven

The strongest claims are the specific aqueous composition and vial or ampoule claims. The broad genus claim has greater theoretical scope but presents more substantial written-description, enablement, obviousness, and claim-construction risk.

Key Takeaways

• US Patent 8,835,501 is a formulation patent centered on HDAC inhibitor solubilization.
• Its principal commercial application is belinostat, the active ingredient in Beleodaq.
• Free arginine, L-arginine, meglumine, and free meglumine are central claim limitations.
• The narrowest commercially important claims cover approximately 50 mg/mL aqueous formulations with an L-arginine-to-bel inostat ratio of 0.8 to 4.
• Vials, ampoules, IV infusion bags, and kits are separately claimed.
• The patent is generally treated as expiring in 2029, subject to the official USPTO term calculation.
• Generic competition proceeds through ANDA and Paragraph IV mechanisms, not biosimilar procedures.
• A formulation design-around using a different solubilizer is the clearest path to reduce infringement exposure.
• The patent is stronger against a copy of Beleodaq's formulation than against a differently formulated belinostat product.

Frequently Asked Questions

Does US Patent 8,835,501 cover belinostat itself?

No. It primarily covers pharmaceutical compositions containing belinostat and specified basic in situ salt formers. A separate compound patent would be required to claim belinostat as a molecule independent of the formulation.

Can a generic belinostat product avoid the patent by removing L-arginine?

Potentially. Removing L-arginine and meglumine may avoid claims requiring those salt formers, but the alternative formulation must be assessed against the broader composition claims and any other belinostat patents.

Does the patent cover oral belinostat tablets?

Claims 25 and 26 include solid dosage forms such as powders, granules, tablets, and lyophilized products. Coverage still requires the claimed HDAC inhibitor and specified basic salt former.

Is US Patent 8,835,501 a method-of-use patent?

No. The claims provided are composition, container, and kit claims. They do not primarily claim treating a disease by administering belinostat.

What FDA pathway applies to a competing belinostat injection?

The relevant pathway is an abbreviated new drug application under section 505(j) of the Federal Food, Drug, and Cosmetic Act. The applicant must address applicable Orange Book patents and establish pharmaceutical equivalence and bioequivalence.

References

1. United States Patent and Trademark Office. (2014). U.S. Patent No. 8,835,501, Pharmaceutical compositions comprising HDAC inhibitors.
2. U.S. Food and Drug Administration. (2023). Beleodaq (belinostat) prescribing information. Acrotech Biopharma, Inc.
3. U.S. Food and Drug Administration. (2014, July 3). FDA approves Beleodaq for treatment of peripheral T-cell lymphoma.
4. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
5. Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 355(j); 35 U.S.C. § 271(e)(2).
6. Spectrum Pharmaceuticals, Inc. (2010). Spectrum Pharmaceuticals and TopoTarget announce U.S. licensing agreement for belinostat.

Drugs Protected by US Patent 8,835,501

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Acrotech Biopharma	BELEODAQ	belinostat	POWDER;INTRAVENOUS	206256-001	Jul 3, 2014		RX	Yes	Yes	8,835,501		Y

Foreign Priority and PCT Information for Patent: 8,835,501

PCT Information
PCT Filed	May 11, 2006	PCT Application Number:	PCT/GB2006/001737
PCT Publication Date:	November 16, 2006	PCT Publication Number:	WO2006/120456

International Family Members for US Patent 8,835,501

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	E542527
Australia	2006245495
Brazil	PI0610128
Canada	2606598
China	101189003
China	102579417