Details for Patent: 8,383,610

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Which drugs does patent 8,383,610 protect, and when does it expire?

Patent 8,383,610 protects NUZYRA and is included in one NDA.

This patent has sixty-five patent family members in twenty-nine countries.

Summary for Patent: 8,383,610

Title:	Salts and polymorphs of 9-(2,2-dimethylpropyl-aminomethyl) minocycline
Abstract:	Crystalline forms, including salts and polymorphs, of a compound useful in the treatment of tetracycline compound-responsive states are provided herein. The crystalline compounds are useful for the treatment or prevention of conditions and disorders such as bacterial infections and neoplasms, as well as other known applications for tetracycline compounds in general.
Inventor(s):	Raymond Cvetovich, Tadeusz Warchol
Assignee:	Paratek Pharmaceuticals Inc
Application Number:	US12/471,758
Patent Claim Types: see list of patent claims	Composition; Compound;

United States Patent 8,383,610: Edoxaban Tosylate Polymorph Claims, Exclusivity and Generic Risk

US Patent No. 8,383,610 protects defined crystalline polymorphs of edoxaban tosylate, the active pharmaceutical ingredient used in Savaysa and Lixiana. The patent does not broadly claim edoxaban, the tosylate salt, or every solid form. Its scope is concentrated on three X-ray powder diffraction-defined polymorphs and pharmaceutical compositions containing those forms. The patent was assigned to Daiichi Sankyo and is listed in the FDA Orange Book for Savaysa.

The principal commercial risk is formulation-specific. A generic applicant that uses a different salt, amorphous material, hydrate, or non-infringing crystalline form may avoid the literal scope of the patent. A product that reproduces one of the claimed XRPD patterns, however, faces a direct infringement risk.

What drug does US Patent 8,383,610 protect?

US Patent 8,383,610 protects polymorphs of edoxaban tosylate. Edoxaban is a direct oral factor Xa inhibitor marketed in the United States as Savaysa and internationally as Lixiana. The FDA-approved product contains edoxaban tosylate, with the labeled strength expressed as the equivalent amount of edoxaban.[2]

The patent’s “Compound 1” is the edoxaban active moiety. The claimed solid forms are salts formed with p-toluenesulfonic acid, commonly called tosylate or tosylate salt.

Item	Patent landscape
Active ingredient	Edoxaban
Salt	Edoxaban tosylate
Drug class	Direct factor Xa inhibitor
U.S. brand	Savaysa
Global brand	Lixiana
Sponsor	Daiichi Sankyo
FDA application	NDA 206316
Patent	US 8,383,610
Technology	Crystalline polymorphs and pharmaceutical compositions

What are the claims of US Patent 8,383,610?

The claims divide into four functional groups:

1. Three polymorph categories defined by XRPD peaks.
2. Subspecies of those polymorphs defined by additional peaks or figures.
3. Process-linked claims covering crystallization from specified solvents.
4. Pharmaceutical composition claims containing the claimed polymorph.

Claim 1 is the independent product claim. It uses a closed Markush formulation, “selected from the group consisting of,” and identifies three alternatives:

• A polymorph with characteristic peaks at approximately 8.06, 13.02, and 18.83 degrees 2θ.
• A polymorph with peaks at approximately 5.11 and 15.60 degrees 2θ.
• A polymorph with peaks at approximately 11.88 and 16.12 degrees 2θ.

The radiation source is Cu Kα. The peak positions are central claim limitations, not merely descriptive analytical data.

How do claims 2 through 10 narrow the polymorph scope?

Claims 2 through 10 narrow the three alternatives in claim 1 by adding more diffraction peaks or incorporating the patent figures.

Claims	Technical limitation	Practical effect
1	Three alternative polymorph classes	Broadest product claim
2-4	Additional peaks or FIG. 8	Narrows the first polymorph class
5-7	Additional peaks or FIG. 10	Narrows the second polymorph class
8-10	Additional peaks or FIG. 9	Narrows the third polymorph class

Claims 2 and 3 add progressively larger sets of peaks to the first polymorph category. Claim 4 references the diffraction pattern in FIG. 8.

Claims 5 and 6 define the second category with additional peaks at approximately 8.89, 10.34, 11.76, 13.70 and 14.81 degrees 2θ. Claim 7 references FIG. 10.

Claims 8 and 9 define the third category with additional peaks at approximately 7.82, 12.68, 18.63, 21.46 and 23.74 degrees 2θ. Claim 10 references FIG. 9.

A material that satisfies claim 2 may also fall within claim 1, but it must satisfy every limitation of claim 2. The dependent claims therefore provide narrower fallback positions rather than separate, independent polymorph families.

What formulations and manufacturing processes are protected?

Claims 11 through 15 link the claimed polymorph to crystallization from particular solvents. They cover material “obtained by crystallizing” edoxaban tosylate from:

• Isopropanol.
• A ketone.
• Acetone, methyl ethyl ketone or methyl pentanone.
• Ethyl acetate.
• Dichloromethane.

These claims are narrower than claim 1 because they add a process history. A generic manufacturer may face two separate questions:

1. Does the isolated material have one of the claimed XRPD patterns?
2. Was it obtained through a process falling within the relevant solvent limitation?

For product-by-process analysis, the product characteristics remain important. A different manufacturing route may not avoid infringement if the resulting material is the same claimed polymorph. Conversely, a process that uses a listed solvent may not infringe if the resulting product does not satisfy the required polymorph limitations.

The patent creates a manufacturing barrier because solvent selection can influence nucleation, crystal packing, particle morphology, residual solvent content and scale-up reproducibility. A process designed around acetone, ethyl acetate, isopropanol or dichloromethane requires solid-form characterization at development, validation and commercial release stages.

What pharmaceutical compositions are protected by the patent?

Claim 16 covers a pharmaceutical composition comprising a polymorph of claim 1 and a pharmaceutically acceptable diluent, excipient or carrier.

Claim 17 narrows claim 16 to a composition in which the polymorph is in pure form. The composition claims could apply to tablets, capsules or other dosage forms if the dosage form contains one of the claimed edoxaban tosylate polymorphs.

The claims do not require a specific excipient, tablet strength, coating, dissolution profile or release mechanism. This gives claims 16 and 17 broader dosage-form coverage than a claim limited to a particular tablet composition. They do not, however, cover every edoxaban formulation independently of the solid form.

How strong is the patent estate for edoxaban?

US 8,383,610 is a focused but commercially relevant patent. Its strength depends on the ability to demonstrate that the accused active ingredient is one of the three claimed crystalline forms.

Strengths

• The independent claim covers three polymorph categories.
• The claim structure includes multiple analytical identifiers.
• Dependent claims provide narrower peak combinations.
• Claims cover pharmaceutical compositions, not only bulk API.
• The patent is directed to the salt used in the marketed product.
• The solid form can be established through routine XRPD analysis.

Limitations

• The claims do not broadly cover all edoxaban salts.
• They do not expressly cover every amorphous form.
• They do not cover every hydrate or solvate unless the material also satisfies the claimed polymorph limitations.
• A generic applicant can attempt a polymorph design-around.
• XRPD peak positions can vary with instrumentation, sample preparation, crystallinity and calibration.
• Claims 11 through 15 are narrower because they require specified crystallization histories.

The patent is therefore stronger against a copy of the marketed edoxaban tosylate solid form than against a deliberately engineered alternative form.

When does edoxaban lose FDA exclusivity and patent protection?

Savaysa received FDA approval on January 8, 2015.[2] As a small-molecule new chemical entity, it received five years of statutory NCE exclusivity, subject to the FDA’s regulatory framework for abbreviated applications. That exclusivity period ended in January 2020.

Patent protection extends beyond regulatory exclusivity. The FDA Orange Book identifies US 8,383,610 for Savaysa with an expiration date of March 14, 2027.[1] The patent’s term is separate from the five-year NCE period.

Milestone	Date or status
Patent priority date	March 14, 2007
Patent issue date	February 26, 2013
FDA Savaysa approval	January 8, 2015
NCE exclusivity	Expired in January 2020
US 8,383,610 expiration	March 14, 2027
Earliest ordinary post-expiration launch	March 15, 2027, subject to other barriers

The final commercial launch date can be earlier if an ANDA applicant brings a successful Paragraph IV challenge and prevails in litigation, reaches a settlement allowing an earlier launch, or obtains authorization based on a non-infringing product and applicable regulatory status.

What is the Orange Book status of US 8,383,610?

US 8,383,610 is listed in the FDA Orange Book for Savaysa. Orange Book listing means the patent is identified by the NDA holder as claiming the approved drug or a method of using the approved drug under the Hatch-Waxman framework.[1]

The listing gives the patent practical importance in ANDA review. A generic applicant must address listed patents through one of the statutory certification pathways:

• 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 patent litigation under 21 U.S.C. § 355(j)(5)(B)(iii). A timely infringement action may impose a 30-month stay on final FDA approval, subject to statutory exceptions and court developments.[3]

Which companies are challenging edoxaban patents?

The patent record and Orange Book listing identify the patent and NDA sponsor, but they do not themselves identify every ANDA filer or establish a Paragraph IV litigation history. No specific Paragraph IV challenger or settlement agreement can be assigned to US 8,383,610 solely from the claims and patent document.

For business analysis, the relevant distinction is between:

• A Paragraph IV challenge directed to US 8,383,610.
• A Paragraph IV challenge directed to a different Savaysa patent.
• A non-infringement strategy based on a different polymorph or salt.
• A post-expiration Paragraph III filing.
• A litigation settlement with a licensed launch date.

These paths produce materially different launch timing and valuation outcomes. A challenge to the polymorph patent would likely require XRPD, thermal analysis, microscopy, solid-state NMR or related evidence comparing the proposed generic API with the claimed forms.

Are biosimilar risks relevant to edoxaban?

No. Edoxaban is a chemically synthesized small molecule, not a biologic. Biosimilar pathways under the Public Health Service Act do not apply. Generic competitors would use the ANDA pathway under section 505(j) of the Federal Food, Drug, and Cosmetic Act.

The relevant competitive risks are:

• Abbreviated new drug applications.
• Paragraph IV patent challenges.
• Polymorph design-arounds.
• Alternative salt or amorphous-form development.
• Authorized generic or license arrangements.
• Foreign-market erosion after local patent expiry.

What generic launch scenarios exist for Savaysa?

Launch after patent expiry

A generic applicant may file with a Paragraph III certification and wait until the March 14, 2027 expiration date, assuming no other blocking patent remains enforceable.

Early launch after a successful Paragraph IV challenge

A successful invalidity, unenforceability or non-infringement case could support launch before patent expiry. The commercial value depends on whether other Orange Book patents independently block approval or create litigation exposure.

Early launch under settlement

Daiichi Sankyo and an ANDA applicant could agree to an authorized launch date before March 2027. The terms would determine whether the entrant receives a license, an authorized generic supply arrangement or another commercial right.

Non-infringing polymorph strategy

A generic applicant could attempt to use an edoxaban form outside the three claim 1 categories. The strategy must account for process claims, analytical overlap, conversion during formulation and possible infringement under the doctrine of equivalents.

How does US 8,383,610 compare with a compound patent?

A compound patent normally protects the active chemical entity or a broad genus of related compounds. US 8,383,610 is narrower because it focuses on solid-state structure.

Patent type	Typical scope	Relevance to edoxaban
Compound patent	Edoxaban or chemical genus	Broadest molecule-level protection
Salt patent	Edoxaban tosylate or another salt	Protects selected salt form
Polymorph patent	Defined crystalline arrangement	Targets commercial API form
Formulation patent	Tablet, capsule, coating or release profile	Targets finished dosage form
Method-of-use patent	Treatment or dosing regimen	Targets clinical use
Process patent	Synthesis or crystallization route	Targets manufacturing

The polymorph patent can remain commercially important after a compound patent expires if the approved product uses the protected form. Its value is highest when the claimed form has superior stability, purity, manufacturability or bioavailability and when generic substitution requires use of the same form.

What geographic coverage exists?

The patent is a United States right. Corresponding patent-family filings may provide protection in other jurisdictions, but each country has separate claim scope, term, validity and enforcement rules. European, Japanese, Chinese and other national rights must be reviewed independently.

The US patent cannot block manufacture, sale or importation in another country unless a corresponding local patent applies. International protection is especially important for edoxaban because Lixiana is marketed outside the United States and regional generic launch dates may differ.

Key Takeaways

• US 8,383,610 is a polymorph patent for edoxaban tosylate.
• Claim 1 covers three XRPD-defined crystalline polymorph categories.
• Claims 2 through 10 add diagnostic peaks or reference patent figures.
• Claims 11 through 15 cover crystallization from specified solvents.
• Claims 16 and 17 cover pharmaceutical compositions containing the claimed polymorph.
• Savaysa’s five-year NCE exclusivity ended in January 2020.
• The Orange Book lists US 8,383,610 with an expiration date of March 14, 2027.
• The patent does not broadly cover every edoxaban salt, amorphous form or hydrate.
• Generic developers may pursue a Paragraph IV challenge or a polymorph design-around.
• Biosimilar law is irrelevant because edoxaban is a small-molecule drug.
• Standalone Savaysa US revenue is not separately disclosed in the cited public materials; commercial exposure is reported within Daiichi Sankyo’s anticoagulant and Lixiana/Savaysa franchise reporting.

FAQs About Edoxaban Tosylate Patent 8,383,610

Does US 8,383,610 cover edoxaban itself?

No. The patent claims selected crystalline polymorphs of edoxaban tosylate. It does not function as a general compound patent for every form of edoxaban.

Can a generic use a different edoxaban salt?

Potentially. A different salt would not literally satisfy a claim directed to a polymorph of edoxaban tosylate, although other patents, regulatory requirements or equivalence theories could remain relevant.

Do the XRPD peaks have to match every listed peak?

A claim must be assessed according to its own limitations. Claim 1 lists minimum identifying peaks for each alternative, while dependent claims require additional peaks or a figure-defined pattern.

Does crystallizing edoxaban tosylate from acetone automatically infringe?

No. Claims 13 and related claims require the claimed polymorph plus the specified crystallization limitation. Solvent use alone does not establish infringement of every claim.

Is an edoxaban generic likely to need a Paragraph IV certification?

If the generic applicant files before the listed patent expires and relies on an ANDA pathway, it generally must address the Orange Book-listed patent through the applicable Hatch-Waxman certification framework.

References

1. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book, Savaysa (NDA 206316).
2. U.S. Food and Drug Administration. (2015). FDA approves Savaysa to reduce the risk of stroke in patients with atrial fibrillation.
3. U.S. Congress. (2023). Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 355(j).
4. United States Patent and Trademark Office. (2013). U.S. Patent No. 8,383,610: Polymorphs of a tosylate salt of Compound 1.
5. Daiichi Sankyo Co., Ltd. (2024). Annual report and product information for Lixiana and Savaysa.

Drugs Protected by US Patent 8,383,610

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Paratek Pharms	NUZYRA	omadacycline tosylate	TABLET;ORAL	209816-001	Oct 2, 2018		RX	Yes	Yes	8,383,610			Y

International Family Members for US Patent 8,383,610

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	075447
Australia	2009248795
Australia	2016262682
Brazil	PI0913026
Canada	2724897