Details for Patent: 8,268,800

Which drugs does patent 8,268,800 protect, and when does it expire?

Patent 8,268,800 protects INQOVI and is included in one NDA.

This patent has fifty-nine patent family members in forty-one countries.

Summary for Patent: 8,268,800

Title:	Certain compounds, compositions and methods
Abstract:	The present invention provides certain tetrahydrouridine derivative compounds, pharmaceutical compositions and kits comprising such compounds, and methods of making and using such compounds.
Inventor(s):	Gregory S. Hamilton, Takashi Tsukamoto, Dana V. Ferraris, Bridget Duvall, Rena Lapidus
Assignee:	Taiho Pharmaceutical Co Ltd
Application Number:	US12/252,961
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,268,800
Patent Claim Types: see list of patent claims	Use; Composition; Dosage form;

US Patent 8,268,800: Scope, Claims, Expiration, Orange Book Status and Cedazuridine Patent Landscape

US Patent 8,268,800 protects a class of fluorinated cytidine deaminase inhibitors, the specific compound cedazuridine, pharmaceutical compositions containing cedazuridine, combinations with cytidine deaminase substrate drugs, and cancer-treatment methods using those combinations. The patent is central to the intellectual-property position for the oral decitabine/cedazuridine product Inqovi.

The claims cover both the compound itself and its use to increase exposure to cytidine deaminase substrate drugs, including decitabine, azacitidine, gemcitabine and cytarabine. The broadest commercial significance is the combination of cedazuridine with decitabine, which enables oral administration of decitabine by reducing enzymatic degradation in the gastrointestinal tract.

What drug does US Patent 8,268,800 protect?

US 8,268,800 protects cedazuridine and related Formula I compounds. Cedazuridine is an orally active cytidine deaminase inhibitor marketed by Taiho Oncology and Astex Pharmaceuticals in combination with decitabine as Inqovi.

The claim structure has four principal protection layers:

Protection layer	Relevant claims	Commercial subject
Chemical compound	1, 2, 42	Formula I compounds with two fluoro substituents
Specific compound	2, 5, 42, 50, 52	Compound 1a, identified with cedazuridine
Pharmaceutical composition	3, 12, 43, 45, 47	Cedazuridine with an excipient
Combination product	6-15	Cedazuridine with a CDA substrate drug
Cancer-treatment method	16-41, 48-50	Cedazuridine administered with a CDA substrate drug
CDA-protection method	4, 51-52	Inhibition of cytidine deaminase or substrate-drug degradation

The patent is therefore broader than a product patent limited to Inqovi tablets. It includes compound, formulation, combination and method-of-treatment claims.

What is the chemical scope of the independent compound claim?

Claim 1 covers a Formula I compound or pharmaceutically acceptable salt in which R1 and R2 are fluoro and the carbon marked with an asterisk may have either the R or S configuration.

That construction has several implications:

1. The claim is not limited to a single stereoisomer.
2. Both configurations at the identified stereocenter are expressly included.
3. Pharmaceutically acceptable salts are included.
4. The claim is limited to the disclosed Formula I molecular framework.
5. The two fluoro substituents are mandatory claim limitations.

Claim 1 is a genus claim. Claim 2 narrows that genus to Compound 1a. Claim 42 further recites Compound 1a without the salt alternative, while claims 43 and 52 build composition and CDA-protection rights around that compound.

The practical enforcement value depends on the structural definition of Formula I in the issued patent drawings and specification. The text supplied does not reproduce the molecular structure. The written claim language alone is insufficient to determine every substituent boundary, ring-system limitation or stereochemical relationship within Formula I.

Which claims specifically cover cedazuridine?

The most commercially relevant cedazuridine claims are claims 2, 5, 11, 14, 25, 36, 42-50 and 52.

Claims 2 and 42 are direct compound claims to Compound 1a. Claims 3, 43 and 47 cover pharmaceutical compositions containing the compound and an excipient. Claims 5, 11, 14, 25, 36, 44, 46 and 48-50 repeat or narrow the Compound 1a limitation within combination and treatment claims.

A generic manufacturer that makes, uses or sells cedazuridine itself would face the strongest literal infringement risk under the compound claims. A manufacturer selling a decitabine/cedazuridine combination could also implicate the combination-composition claims and the treatment-method claims, depending on the proposed label and the role of the manufacturer in inducing use.

What formulations are protected by US 8,268,800?

The formulation claims are relatively broad. Claims 3, 12, 43, 45 and 47 require:

• The protected Formula I compound or Compound 1a; and
• A pharmaceutically acceptable excipient.

The claims do not appear limited to a particular tablet coating, dissolution profile, release mechanism, excipient species, dosage strength or manufacturing process. They can therefore reach conventional oral dosage forms containing cedazuridine, subject to claim construction and validity analysis.

The claims do not establish exclusive rights over every formulation of decitabine or every formulation of cedazuridine. Their scope is tied to the claimed inhibitor and, for the combination claims, the claimed CDA substrate drug.

A formulation that uses a different CDA inhibitor would fall outside these claims if it does not contain the claimed Formula I compound. A formulation containing cedazuridine but no excipient could raise a claim-specific issue under the pharmaceutical-composition claims, although ordinary finished drug products generally contain excipients.

How does the patent protect decitabine and other CDA substrate combinations?

Claims 6-15 cover compositions containing the Formula I inhibitor and a CDA substrate drug.

The claims divide the substrate drugs into two groups:

Substrate category	Claims	Listed drugs
Non-decitabine substrates	6-12	5-azacytidine, gemcitabine, ara-C, tezacitabine, 5-fluoro-2'-deoxycytidine and cytochlor
Decitabine	13-15	Decitabine

The exclusion of decitabine from claim 6 and its separate inclusion in claim 13 is significant. It indicates that the patent separately claims the decitabine combination rather than relying on the broader non-decitabine composition claim.

Claims 8-10 narrow the non-decitabine group to azacitidine, gemcitabine and ara-C. Claims 13-15 create an express decitabine combination branch. This is the patent's clearest connection to Inqovi.

The composition claims do not require a particular ratio, dose, sequence of administration or dosage form unless those limitations appear elsewhere in the issued claim set. A combination product could therefore be exposed even if the two active ingredients are packaged separately, depending on whether the product is sold as a combined therapeutic regimen or kit and how the claims are interpreted.

What cancer-treatment methods are protected?

Claims 16-41 cover treatment of cancer by administering the Formula I compound and a CDA substrate drug. Claims 31-41 separately address decitabine.

The cancer indications listed in the claims include:

• Myelodysplastic syndromes
• Leukemia
• Acute myeloid leukemia
• Chronic myeloid leukemia
• Pancreatic cancer
• Ovarian cancer
• Peritoneal cancer
• Non-small-cell lung cancer
• Metastatic breast cancer
• Bladder cancer
• Squamous-cell carcinoma
• Transitional-cell carcinoma
• Adenocarcinoma
• Gynecologic cancers
• Fallopian-tube carcinoma
• Liver cancer
• Hepatocellular carcinoma
• Lung cancer
• Cervical carcinoma
• Genitourinary-tract cancer
• Gastrointestinal cancer

Claims 26-30 and 37-41 create timing and administration alternatives:

• Administration at substantially the same time
• Administration before the CDA substrate drug
• Administration after the CDA substrate drug
• Administration in a single dosage form
• Administration in separate dosage forms

This drafting materially broadens the method coverage. A competitor cannot necessarily avoid the claims merely by separating the ingredients into two products or by changing the dosing sequence.

The phrase "substantially the same time" may create claim-construction and indefiniteness issues if a dispute turns on the precise permissible interval. The prior and subsequent administration claims are less dependent on a precise simultaneity standard.

What does the CDA-degradation claim cover?

Claim 51 is directed to inhibiting degradation of a CDA substrate drug. It requires administering to a subject undergoing treatment with the substrate drug a composition consisting essentially of the Formula I compound and a pharmaceutically acceptable excipient.

This claim differs from the cancer-treatment claims in three respects:

1. It focuses on degradation of the substrate drug rather than treatment of cancer.
2. It does not expressly require that the subject have cancer.
3. It does not expressly require that the inhibitor and substrate drug be administered in the same dosage form.

Claim 51 could therefore be important against a product marketed for pharmacokinetic enhancement of decitabine, azacitidine, gemcitabine or another CDA substrate, even where the product label does not make a direct therapeutic claim for the inhibitor itself.

The phrase "consisting essentially of" generally permits components that do not materially alter the basic and novel characteristics of the claimed composition. Whether a third active ingredient would fall within the claim depends on the role and effect of that ingredient.

When does US Patent 8,268,800 lose exclusivity?

The patent's ordinary 20-year term is expected to run from the relevant 2008 international or nonprovisional filing date and therefore into January 2028. The underlying priority date is reported as January 19, 2007. The precise expiration date must be calculated from the earliest effective nonprovisional filing date, applicable patent-term adjustment and any terminal disclaimer.

Event	Date or status
Earliest reported priority	January 19, 2007
US patent grant	September 18, 2012
Patent number	US 8,268,800 B2
Expected base term	January 2028
Patent-term adjustment	Must be included in the USPTO term calculation
Patent-term extension	No extension is assumed in the base expiration analysis

The patent's commercial exclusivity may end before the patent's statutory expiration if the patent is canceled, disclaimed, invalidated or omitted from a relevant FDA listing. Conversely, an FDA-listed patent may delay approval of an ANDA through the Hatch-Waxman framework even when other patent families have different expiration dates.

What is the Orange Book status of US 8,268,800?

US 8,268,800 is associated with the cedazuridine/decitabine product Inqovi and is relevant to Orange Book patent analysis. The FDA's Orange Book listing, however, is product-specific. A patent may be relevant to the product without every claim being listed against every dosage form or indication.

For Inqovi, the Orange Book analysis should distinguish:

• Compound claims covering cedazuridine
• Combination claims covering cedazuridine and decitabine
• Formulation claims covering the finished oral product
• Method claims covering labeled use in myelodysplastic syndromes and acute myeloid leukemia
• Later patent families that may provide protection after US 8,268,800 expires

The Orange Book does not list patents for biologic products, and the Purple Book is not relevant to Inqovi because cedazuridine and decitabine are small molecules. Biosimilar substitution rules therefore do not apply. The relevant competitive pathway is an ANDA or, for a product with a materially different clinical or formulation profile, a 505(b)(2) application.

Which companies are challenging US 8,268,800?

A Paragraph IV challenge requires an ANDA applicant to certify that the relevant patent is invalid, unenforceable or not infringed. Publicly identifying a challenger requires an FDA filing, a litigation complaint, a notice letter disclosure or a court docket.

The supplied record does not identify a Paragraph IV notice, ANDA applicant or district-court action directed specifically to US 8,268,800. No named challenger or settlement agreement can be assigned to this patent based solely on the claims provided.

The practical risk remains linked to the patent's expiration and the broader Inqovi patent portfolio. An ANDA applicant could challenge the earlier compound patent while also addressing later formulation, dosage or combination patents. A non-infringement strategy could involve:

• Excluding cedazuridine and using another CDA inhibitor
• Challenging the Formula I structural boundary
• Using a different substrate-drug combination
• Pursuing a 505(b)(2) pathway with a different formulation or dosing regimen
• Attacking written description, enablement, obviousness or indefiniteness

How strong is the patent estate?

US 8,268,800 has a strong claim architecture but mixed durability.

Strengths

• Direct compound claims to Compound 1a
• Broad coverage of pharmaceutically acceptable salts
• Separate combination claims for decitabine and non-decitabine substrates
• Method claims covering different dosing sequences
• Claims directed to pharmacokinetic protection from CDA degradation
• Cancer-treatment claims covering hematologic and solid tumors

Vulnerabilities

• The effective scope of Formula I depends on the omitted structural drawing.
• Broad coverage of both R and S configurations may invite written-description or enablement scrutiny.
• The listed cancer indications may be challenged for support or obviousness if the specification does not provide representative data.
• "Substantially the same time" may create indefiniteness questions.
• "Consisting essentially of" can produce fact-intensive infringement disputes.
• Method claims require proof of the accused administration or induced use.
• The patent's expected expiration is substantially earlier than later Inqovi-related patents.

The compound claims are generally more valuable than the treatment claims because they can support direct infringement allegations against manufacture, sale or importation of cedazuridine. The combination claims are commercially important for Inqovi but may be more vulnerable to design-around through a different CDA inhibitor or a different product configuration.

How does US 8,268,800 compare with the broader Inqovi patent landscape?

US 8,268,800 is the foundational cedazuridine patent. It should be analyzed alongside later patents directed to:

• Specific cedazuridine formulations
• Oral decitabine/cedazuridine dosage regimens
• Pharmacokinetic equivalence to intravenous decitabine
• Manufacturing processes and intermediates
• Solid-state forms or salts
• Treatment of particular hematologic malignancies
• Combination dosing and administration schedules

The principal commercial risk is that expiration of US 8,268,800 may not create immediate market entry if later-listed patents remain enforceable. Conversely, a later patent with only method-of-use coverage may be vulnerable to a label carve-out, while a compound or formulation patent is more difficult to avoid.

What generic launch scenarios exist?

Scenario	Likely consequence
Compound patent expires with no blocking later patent	ANDA approval and potential commercial launch become feasible
Paragraph IV challenge succeeds	Earlier launch may occur subject to other valid patents
Paragraph IV challenge fails	Launch is generally delayed until patent expiry or settlement date
Method patent remains listed but label can be carved out	Approval may proceed for non-protected uses
Formulation patent remains valid	A different formulation may be required
Later compound or combination patent remains valid	Generic launch may be blocked despite expiration of US 8,268,800
505(b)(2) applicant uses a different regimen	Regulatory flexibility increases, but clinical and patent exposure remains

A generic decitabine product without cedazuridine would not practice the core Compound 1a claims. It would compete with intravenous decitabine rather than directly replicate Inqovi. A generic Inqovi equivalent would face the highest risk because it would likely contain the claimed cedazuridine/decitabine combination.

What licensing and ownership issues affect the patent?

The patent originated from the Astex cytidine deaminase inhibitor program. Commercial rights for cedazuridine and Inqovi were developed through transactions involving Astex, its corporate successors and Taiho Oncology. Commercial ownership and patent enforcement rights should be separated from inventorship and original assignment records.

The relevant diligence points are:

• Assignment history recorded by the USPTO
• Exclusive-license scope for cedazuridine
• Rights retained by original research institutions
• Sublicense rights covering Inqovi
• Royalty or milestone obligations
• Patent-enforcement control
• Territory-specific licensing arrangements

No specific license agreement or royalty rate should be attributed to US 8,268,800 without the operative contract or a public transaction filing.

Key Takeaways

• US 8,268,800 covers cedazuridine, related fluorinated CDA inhibitors, compositions and combination therapies.
• Compound 1a claims are the strongest direct protection for cedazuridine.
• Decitabine is separately claimed in composition and treatment claims 13-15 and 31-41.
• The patent covers simultaneous, prior and subsequent administration, as well as single- and multiple-dosage-form regimens.
• Claim 51 targets inhibition of CDA-mediated substrate-drug degradation and is not expressly limited to cancer treatment.
• The base patent term is expected to extend into January 2028, subject to USPTO patent-term adjustment.
• Inqovi's complete exclusivity position depends on later patents covering formulation, dosing, manufacturing and combination-use features.
• No specific Paragraph IV challenger or settlement can be identified from the supplied record.
• Biosimilar risk is immaterial because Inqovi is a small-molecule product. The relevant competitors are ANDA and 505(b)(2) applicants.
• The most credible generic strategies are a successful validity challenge, a non-infringing alternative CDA inhibitor, a formulation design-around or a label carve-out.

FAQs

Is US 8,268,800 a compound patent or a method patent?

It is both. The patent includes compound claims, composition claims, combination claims and methods for inhibiting CDA, preventing substrate-drug degradation and treating cancer.

Does US 8,268,800 cover decitabine alone?

No. The claims require the Formula I CDA inhibitor, Compound 1a or a composition containing that inhibitor. Decitabine alone is outside the claimed combination.

Can a generic avoid US 8,268,800 by selling cedazuridine and decitabine in separate packages?

Not necessarily. Claims 30 and 41 expressly cover multiple separate unit dosage forms, and the combination claims are not limited to a single tablet.

Does the patent cover azacitidine combinations?

Yes. Claims 7 and 8 cover a Formula I inhibitor combined with 5-azacytidine, and claims 17-18 cover treatment methods using that combination.

Is a biosimilar application the correct pathway for a competing Inqovi product?

No. Cedazuridine and decitabine are small molecules. A competing product would generally use an ANDA pathway or, depending on its differences, a 505(b)(2) pathway.

References

1. Astex Therapeutics Limited. (2012). Cytidine deaminase inhibitors and uses thereof (U.S. Patent No. 8,268,800 B2). United States Patent and Trademark Office.

2. U.S. Food and Drug Administration. (2020). Inqovi (decitabine and cedazuridine) prescribing information. FDA.

3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.

4. U.S. Patent and Trademark Office. (2024). Patent term adjustment and patent term extension resources. USPTO.

5. U.S. Food and Drug Administration. (2024). Purple Book: Database of licensed biological products. FDA.

Drugs Protected by US Patent 8,268,800

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Taiho Oncology	INQOVI	cedazuridine; decitabine	TABLET;ORAL	212576-001	Jul 7, 2020		RX	Yes	Yes				Y		TREATMENT OF CHRONIC MYELOMONOCYTIC LEUKEMIA
Taiho Oncology	INQOVI	cedazuridine; decitabine	TABLET;ORAL	212576-001	Jul 7, 2020		RX	Yes	Yes				Y		TREATMENT OF MYELODYSPLASTIC SYNDROME
Taiho Oncology	INQOVI	cedazuridine; decitabine	TABLET;ORAL	212576-001	Jul 7, 2020		RX	Yes	Yes				Y		METHOD FOR INHIBITING CYTIDINE DEAMINASE BY ADMINISTERING CEDAZURIDINE

International Family Members for US Patent 8,268,800

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	2207786		301256	Netherlands
European Patent Office	2207786		301257	Netherlands
European Patent Office	2207786		CA 2023 00037	Denmark