Details for Patent: 12,465,586

Which drugs does patent 12,465,586 protect, and when does it expire?

Patent 12,465,586 protects CERDELGA and is included in one NDA.

This patent has one hundred and twelve patent family members in forty countries.

Summary for Patent: 12,465,586

Title:	Inhibitors of glucosylceramide synthase
Abstract:	The hemitartrate salt of a compound represented by the following structural formula: (Formula I Hemitartrate), which may be used in pharmaceutical applications, are disclosed. Particular single crystalline forms of the Formula (I) Hemitartrate are characterized by a variety of properties and physical measurements. As well, methods of producing crystalline Formula (I) Hemitartrate, and using it to inhibit glucosylceramide synthase or lowering glycosphingolipid concentrations in subjects to treat a number of diseases, are also discussed. Pharmaceutical compositions are also described.
Inventor(s):	Hanlan Liu, Chris Willis, Renu Bhardwaj, Jianmei Kochling, Judith Peterschmitt, Craig Siegel
Assignee:	Genzyme Corp
Application Number:	US17/865,195
Patent Claim Types: see list of patent claims	Use; Dosage form;

United States Patent 12,465,586: Scope, Claims, Exclusivity and Patent Landscape for Eliglustat Hemitartrate in Gaucher Disease

U.S. Patent No. 12,465,586 covers genotype-directed treatment of type 1 Gaucher disease using a specified crystalline hemitartrate salt of the compound identified as formula (I), at a 100 mg dose. The claims divide patients by CYP2D6 metabolizer status: poor metabolizers receive 100 mg once daily, while intermediate and extensive metabolizers receive 100 mg twice daily. The patent also requires a solid-state form identified by at least three of six Cu Kα X-ray powder diffraction peaks.

The patent is narrower than a basic compound or composition patent but potentially difficult to design around if a marketed product uses the claimed salt form, dose, capsule, and genotype-directed regimen. Its principal commercial value is method-of-use protection tied to pharmacogenomic dosing and formulation identity.

What drug and active ingredient does U.S. Patent 12,465,586 cover?

The claimed therapy is directed to the active compound used in Cerdelga, the Sanofi/Genzyme treatment for adults with type 1 Gaucher disease. The compound is generally identified in the commercial and regulatory record as eliglustat, administered as eliglustat tartrate.[2]

The supplied claims do not reproduce the chemical structure of formula (I). The scope therefore depends on the formula and definitions contained in the patent specification and incorporated claim construction. Based on the disease indication, CYP2D6 dosing scheme, and salt description, the patent concerns eliglustat hemitartrate or a defined crystalline form of that salt.

The claims do not cover every eliglustat product or every treatment of Gaucher disease. They require the following combination:

1. A human patient with type 1 Gaucher disease.
2. CYP2D6 status determined by genotyping.
3. A specified metabolizer classification.
4. Administration of the hemitartrate salt of formula (I).
5. A 100 mg dose.
6. In claims 2 through 7, an oral once-daily or twice-daily regimen.
7. In claims 3, 5 and 7, a capsule.
8. In every independent claim, a defined XRPD signature.

What are the independent claims in U.S. Patent 12,465,586?

Claims 1, 4 and 6 are the independent claims.

Claim	CYP2D6 group	Dose	Frequency	Dosage form	XRPD limitation
1	Poor metabolizer	100 mg	Not expressly specified	Not specified	At least 3 of 6 listed peaks
4	Intermediate metabolizer	100 mg	Twice daily	Oral dosage form	At least 3 of 6 listed peaks
6	Extensive metabolizer	100 mg	Twice daily	Oral dosage form	At least 3 of 6 listed peaks

Dependent claims narrow the regimen further:

Dependent claim	Added limitation
2	Claim 1 administered orally once per day
3	Claim 2 administered as a capsule
5	Claim 4 administered as a capsule
7	Claim 6 administered as a capsule

The claim set does not include a separate ultra-rapid-metabolizer category. It also does not expressly recite an intermediate metabolizer receiving a once-daily dose or a poor metabolizer receiving twice-daily dosing.

What formulation and crystal-form features are protected?

The salt must be characterized by at least three XRPD peaks selected from the following six positions:

• 5.1°
• 6.6°
• 10.7°
• 11.0°
• 15.9°
• 21.7°

Each peak is defined as the stated value plus or minus 0.2°, and the measurement must use Cu Kα radiation.

This is a solid-state limitation. The claim does not require all six peaks. Any combination of at least three of the six listed reflections can satisfy the limitation, subject to the specification's interpretation of "at least three" and the quality and methodology of the XRPD test.

Why the XRPD limitation matters

The XRPD requirement can limit infringement to a particular polymorph, hydrate, solvate, or crystalline salt form. A generic or follow-on manufacturer could attempt to avoid literal infringement by using:

• A different salt of the compound.
• The free base rather than the hemitartrate.
• An amorphous form.
• A different polymorph that does not produce at least three of the claimed peaks.
• A formulation in which the claimed crystalline form is absent or materially transformed.

Those alternatives would not necessarily avoid infringement if the product contains the claimed form at manufacture or if the patent's claims or specification support an equivalent form theory. Solid-state patents therefore require laboratory characterization of the drug substance and finished dosage form.

How broad is the CYP2D6 method-of-use coverage?

The patent claims pharmacogenomic treatment, not merely administration of eliglustat.

A claimant would need to prove that the patient was assessed as a poor, intermediate, or extensive CYP2D6 metabolizer by genotyping. A patient treated empirically without genotype testing may fall outside the literal wording, depending on the evidence and claim construction. Conversely, an electronic medical record, laboratory report, or prescribing protocol documenting CYP2D6 genotyping could support the assessment element.

The claims are strongest against a product label or treatment protocol that expressly instructs:

• CYP2D6 genotyping;
• classification by metabolizer status;
• 100 mg dosing;
• the claimed frequency; and
• use of the claimed hemitartrate crystal form.

The claims are weaker against off-label treatment where the prescriber does not perform genotyping or does not follow the claimed dose. They may also be difficult to enforce against a manufacturer if the proposed label omits the patented method and the manufacturer has no active role in patient-specific treatment.

How does the patented dose compare with the FDA-approved Cerdelga dose?

The FDA-approved Cerdelga labeling identifies CYP2D6-based dosing and restrictions. The approved commercial capsule strength is generally identified as 84 mg eliglustat, administered according to metabolizer status.[2]

The supplied patent claims a 100 mg effective amount of the hemitartrate salt. That distinction is important because salt weight and active-moiety weight are not interchangeable. A 100 mg amount of eliglustat hemitartrate may correspond to a different amount of eliglustat free base or active moiety than a capsule labeled as 84 mg eliglustat.

Issue	U.S. Patent 12,465,586	Cerdelga regulatory labeling
Disease	Type 1 Gaucher disease	Type 1 Gaucher disease
Pharmacogenomic factor	CYP2D6 genotype and metabolizer status	CYP2D6 genotype and metabolizer status
Claimed poor-metabolizer dose	100 mg once daily under claims 1-3	Label uses a different commercial strength and dosing presentation
Claimed intermediate-metabolizer dose	100 mg twice daily	Label-based genotype-directed dosing
Claimed extensive-metabolizer dose	100 mg twice daily	Label-based genotype-directed dosing
Dosage form	Oral dosage form; capsule in dependent claims	Capsule
Solid form	Specified hemitartrate XRPD pattern	Product-specific composition and manufacturing information

A literal infringement analysis must compare the patent's 100 mg limitation with the exact basis on which the product dose is expressed. A product labeled 84 mg eliglustat is not automatically identical to a product containing 100 mg of eliglustat hemitartrate.

What patents protect Cerdelga and eliglustat?

The eliglustat estate has several distinct patent categories:

Patent category	Typical subject matter	Relevance to U.S. Patent 12,465,586
Basic compound patents	Eliglustat chemical structure and analogs	Potentially earlier foundational protection
Salt and solid-state patents	Tartrate or hemitartrate salts, polymorphs, XRPD profiles	Directly relevant
Formulation patents	Capsules, excipients, release characteristics, dosage forms	Relevant to claims 3, 5 and 7
Method-of-use patents	Treatment of Gaucher disease	Relevant to disease indication
Pharmacogenomic patents	CYP2D6 testing and dose selection	Directly relevant
Manufacturing patents	Crystallization, purification, salt formation and scale-up	May create supply-chain barriers
Regulatory exclusivity	NDA exclusivity and pediatric exclusivity	Separate from patent rights

Patent No. 12,465,586 appears to occupy the intersection of solid-state protection and CYP2D6-directed treatment. It is therefore more specific than a basic eliglustat patent but potentially more commercially aligned with the labeled product and its prescribing algorithm.

A complete freedom-to-operate review must examine the entire family, continuation applications, divisional applications, terminal disclaimers, reexaminations, post-grant proceedings and Orange Book submissions. The grant number alone does not establish the full family scope.

What is the Orange Book status of U.S. Patent 12,465,586?

The Orange Book status must be determined from the current FDA Approved Drug Products with Therapeutic Equivalence Evaluations database and the relevant NDA patent-transmission records.[3]

An issued patent is not automatically an Orange Book-listed patent. Listing depends on whether the NDA holder submitted the patent and whether FDA accepted it for listing. Method-of-use patents may be listed when they claim an approved method of using the drug, while patents directed solely to manufacturing processes generally are not listed.[3]

For this patent, the principal Orange Book questions are:

• Whether it was submitted against the Cerdelga NDA.
• Whether FDA accepted it as a method-of-use or drug-product patent.
• Whether the listed use corresponds to the approved Gaucher disease indication.
• Whether the listing contains a use code that a generic applicant can carve out.
• Whether the patent was listed before or after an ANDA was filed.

The claim language is commercially relevant to Orange Book listing because it recites an approved disease, an approved active ingredient, dosage instructions and a dosage form. Its XRPD limitation may create a listing issue if FDA views the patent as directed primarily to a particular solid form rather than the approved drug product.

When does U.S. Patent 12,465,586 lose exclusivity?

The patent's statutory expiration is generally determined by the earliest effective nonprovisional U.S. filing date in the priority chain, subject to patent-term adjustment, patent-term extension, terminal disclaimers and any applicable statutory adjustment.[5]

The supplied claim text does not identify:

• The earliest priority application.
• The U.S. nonprovisional filing date.
• Any patent-term adjustment.
• Any terminal disclaimer.
• Any patent-term extension.
• Whether the patent is a continuation with a different effective filing date.

Accordingly, an exact expiration date cannot be established from the claim text alone. Patent term is not determined by the issue date of U.S. Patent 12,465,586. The controlling record is the USPTO patent data and the face of the issued patent.[5]

Regulatory exclusivity is separate. Cerdelga's NDA exclusivity period, if any remains, does not extend the patent term, and expiration of a patent does not eliminate an independent period of FDA exclusivity.[3]

What Paragraph IV challenges could target this patent?

A generic applicant seeking approval before patent expiration could file an ANDA with a Paragraph IV certification if the patent is listed in the Orange Book and the applicant asserts that the patent is invalid, unenforceable or will not be infringed.[6]

Potential challenge theories include:

Lack of infringement

A challenger could argue that its product does not contain the claimed hemitartrate crystal form or does not show at least three of the six required XRPD peaks. It could also argue that:

• The product contains a different salt.
• The dose is expressed on a different mass basis.
• The proposed label does not require CYP2D6 genotyping.
• The label does not instruct the patented dose or frequency.
• The proposed product is not a capsule where the dependent claims are asserted.

Anticipation

An anticipation challenge would require a single prior-art reference to disclose every element, including the specific CYP2D6 subgroup, 100 mg dose, dosage frequency, hemitartrate form and XRPD limitations.[6]

Obviousness

The strongest validity challenge may be obviousness based on the combination of:

• Known eliglustat pharmacokinetics.
• CYP2D6 genotype-based dosing.
• Known Gaucher treatment regimens.
• A known eliglustat tartrate or hemitartrate form.
• Routine solid-state characterization.

The patent owner would likely argue that the specific 100 mg regimen and selected crystalline form were not predictable as a clinically effective combination, particularly across different CYP2D6 phenotypes.

Written description and enablement

The claims cover any combination of at least three peaks from six listed reflections. A challenger could test whether the specification adequately supports the breadth of that alternative combination and whether the full claimed patient-dosing matrix is enabled without undue experimentation.

Indefiniteness

Potential issues include the meaning of:

• "Effective amount" when the amount is stated as 100 mg.
• The mass basis for the hemitartrate salt.
• "At least three" peaks when peak intensity and analytical conditions can vary.
• Whether a peak within plus or minus 0.2° is sufficient without intensity or relative-intensity requirements.
• The boundaries between CYP2D6 phenotype categories.

What generic launch scenarios exist?

Three launch scenarios are commercially plausible.

Scenario	Product or label strategy	Main risk
Full-label launch after expiry	Generic copies the approved regimen and product form	Direct exposure to method and formulation claims
Skinny-label launch	Generic removes the patented genotype-directed use if legally permissible	Induced-infringement and regulatory carve-out disputes
Alternative-form launch	Generic uses a nonclaimed salt or polymorph	Bioequivalence, stability and formulation-development risk

A skinny label may reduce risk only if the carved-out use is legally separable from the remaining approved uses and the generic's conduct does not encourage the patented treatment. The availability of a carve-out depends on the FDA use code, label content and the actual market behavior of the generic sponsor.[3,6]

How strong is the patent estate?

The patent has moderate-to-strong practical scope against a directly substitutable product, but its legal breadth is narrower than the commercial importance of the drug.

Strength factor	Assessment
Clinical relevance	High because claims track CYP2D6-directed dosing
Chemical breadth	Low to moderate because the claims require a specified salt
Solid-state specificity	High; XRPD limits the claimed form
Label-read-through risk	Moderate to high if the generic label mirrors genotype-based dosing
Design-around potential	Moderate through salt, polymorph, dose-basis or label changes
Enablement vulnerability	Fact-dependent and potentially material
Orange Book leverage	Depends on FDA listing and use-code treatment
Biosimilar relevance	None; eliglustat is a small molecule, not a biologic
Manufacturing barrier	Potentially meaningful if the claimed form is required for stability or bioavailability

Which companies are challenging eliglustat exclusivity?

The principal branded-interest holder is Sanofi through Genzyme, the developer and marketer associated with Cerdelga.[2] The supplied information does not identify an active Paragraph IV filer, ANDA litigation, inter partes review, post-grant review or settlement involving U.S. Patent 12,465,586.

No biosimilar pathway applies. Eliglustat is a chemically synthesized small molecule regulated through the ANDA pathway, not the Biologics Price Competition and Innovation Act pathway.[4,6]

What litigation and licensing issues affect the patent?

The claim text does not establish any pending litigation, settlement agreement or license involving U.S. Patent 12,465,586. A patent assignment to Sanofi, Genzyme or an affiliate would not by itself prove a third-party license or settlement.

The principal litigation risks are likely to arise in four areas:

1. ANDA litigation after a Paragraph IV notice.
2. Claim construction concerning the XRPD peak requirement.
3. Dose-basis disputes concerning 100 mg of salt versus active moiety.
4. Induced infringement disputes involving genotype-directed labeling.

The most important diligence point is whether the patent is part of a broader continuation family. A continuation could preserve similar dosing or formulation claims after an earlier patent expires or is narrowed.

Key Takeaways

• U.S. Patent 12,465,586 claims genotype-directed treatment of type 1 Gaucher disease using a defined hemitartrate crystal form of the compound of formula (I).
• Claims 1 through 3 cover poor CYP2D6 metabolizers treated with 100 mg once daily.
• Claims 4 and 5 cover intermediate metabolizers treated with 100 mg twice daily.
• Claims 6 and 7 cover extensive metabolizers treated with 100 mg twice daily.
• The salt must show at least three of six specified Cu Kα XRPD peaks within plus or minus 0.2°.
• The patent is a method-of-use and solid-state patent, not a broad basic-compound claim based on the supplied language.
• Literal infringement depends on the exact salt, crystal form, dose basis, genotyping process, metabolizer classification and label instructions.
• Eliglustat is a small molecule, so biosimilar competition is not relevant.
• Generic competition would proceed through ANDA certification, with possible Paragraph IV and skinny-label strategies.
• The exact expiration date and current Orange Book listing cannot be determined from the claim text alone.
• The principal commercial risk is a generic or follow-on product that copies both the CYP2D6 dosing algorithm and the claimed hemitartrate crystal form.

Frequently Asked Questions

Does a product containing eliglustat automatically infringe U.S. Patent 12,465,586?

No. The accused product and treatment must satisfy the claimed salt, XRPD, dose, patient genotype and dosing limitations. Eliglustat alone is not enough.

Can a generic avoid the patent by using a different polymorph?

Potentially. A polymorph that does not satisfy the required XRPD limitation may avoid literal infringement, but bioequivalence, stability, equivalence and doctrine-of-equivalents issues would remain.

Is 100 mg the same as the marketed 84 mg Cerdelga capsule?

Not necessarily. The comparison depends on whether each amount is expressed as eliglustat active moiety, eliglustat free base or the hemitartrate salt.

Does CYP2D6 testing have to occur before treatment?

The claims require that the patient be assessed as a poor, intermediate or extensive metabolizer as determined by CYP2D6 genotyping. The timing and evidentiary requirements would depend on the patent specification and claim construction.

Can a generic omit the patented Gaucher dosing instructions from its label?

A generic may pursue a regulatory carve-out where the patented use is legally separable and FDA permits the omission. The sponsor can still face infringement allegations if its label, marketing or conduct encourages the patented use.

References

1. U.S. Patent No. 12,465,586, claims 1-7. United States Patent and Trademark Office.
2. U.S. Food and Drug Administration. (2024). Cerdelga (eliglustat tartrate) prescribing information. FDA.
3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. FDA.
4. U.S. Food and Drug Administration. (2024). Table of pharmacogenetic associations. FDA.
5. United States Patent and Trademark Office. (2024). Patent term adjustment and patent term calculation guidance. USPTO.
6. 21 U.S.C. § 355(j); 35 U.S.C. §§ 271(e), 282.

Drugs Protected by US Patent 12,465,586

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Genzyme Corp	CERDELGA	eliglustat tartrate	CAPSULE;ORAL	205494-001	Aug 19, 2014	AB	RX	Yes	Yes	12,465,586					LONG-TERM TREATMENT OF ADULTS WITH GAUCHER DISEASE TYPE 1 WHO ARE CYP2D6 POOR METABOLIZERS WITH 84 MG ONCE DAILY OF ELIGLUSTAT (EQUIVALENT TO 100 MG OF ELIGLUSTAT TARTRATE)
Genzyme Corp	CERDELGA	eliglustat tartrate	CAPSULE;ORAL	205494-001	Aug 19, 2014	AB	RX	Yes	Yes	12,465,586					LONG-TERM TREATMENT OF ADULTS WITH GAUCHER DISEASE TYPE 1 WHO ARE CYP2D6 EXTENSIVE OR INTERMEDIATE METABOLIZERS WITH 84 MG TWICE PER DAY OF ELIGLUSTAT (EQUIVALENT TO 100 MG OF ELIGLUSTAT TARTRATE TWICE PER DAY)

International Family Members for US Patent 12,465,586

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	079152
Argentina	121611
Argentina	121612
Australia	2010324810
Australia	2016202591
Australia	2017265180
Brazil	112012012947