Details for Patent: 9,624,152

Summary for Patent: 9,624,152

Title:	Hydroxyl compounds and compositions for cholesterol management and related uses
Abstract:	The present invention relates to novel hydroxyl compounds, compositions comprising hydroxyl compounds, and methods useful for treating and preventing a variety of diseases and conditions such as, but not limited to aging, Alzheimer's Disease, cancer, cardiovascular disease, diabetic nephropathy, diabetic retinopathy, a disorder of glucose metabolism, dyslipidemia, dyslipoproteinemia, hypertension, impotence, inflammation, insulin resistance, lipid elimination in bile, obesity, oxysterol elimination in bile, pancreatitis, pancreatitius, Parkinson's disease, a peroxisome proliferator activated receptor-associated disorder, phospholipid elimination in bile, renal disease, septicemia, metabolic syndrome disorders (e.g., Syndrome X), thrombotic disorder. Compounds and methods of the invention can also be used to modulate C reactive protein or enhance bile production in a patient. In certain embodiments, the compounds, compositions, and methods of the invention are useful in combination therapy with other therapeutics, such as hypocholesterolemic and hypoglycemic agents.
Inventor(s):	Jean-Louis H. Dasseux, Carmen D. Oniciu
Assignee:	Esperion Therapeutics Inc
Application Number:	US14/674,028
Patent Claim Types: see list of patent claims	Use; Composition; Delivery;

United States Patent 9,624,152: Claim Scope, Bempedoic Acid Coverage, and Patent Landscape

U.S. Patent No. 9,624,152 is a method-of-use patent covering administration of sterol-synthesis-inhibiting compounds, including the bempedoic-acid chemical space, in a pharmaceutical composition. Its strongest commercial relevance is to oral bempedoic acid products such as Nexletol and Nexlizet. The patent does not claim a compound or composition in isolation. It claims a treatment method that requires administration to a patient, a therapeutically effective amount, a pharmaceutical vehicle, and inhibition of sterol synthesis.

The broadest claim is structurally expansive but functionally constrained. Claims 3 through 7 narrow the Markush genus toward a specific dicarboxylic-acid species. Claims 8 and 9 appear to identify particular compounds, but the chemical structures were not included in the supplied text and cannot be mapped precisely from the claim transcription alone.

What does U.S. Patent 9,624,152 claim?

Claim 1 covers:

1. A patient-treatment method;
2. Administration of a pharmaceutical composition;
3. A therapeutically effective amount;
4. A compound within a defined formula-I genus or a pharmaceutically acceptable salt;
5. A result of inhibiting sterol synthesis.

The claim has both structural and functional limitations. A product or treatment would need to satisfy both.

Claim element	Scope
Disease or condition	No specific disease is recited
Patient	“Patient in need thereof”
Administration	Required, but route is not limited in claim 1
Amount	Therapeutically effective amount
Dosage form	Pharmaceutical composition with a pharmaceutically acceptable vehicle
Active ingredient	Compound of formula I or pharmaceutically acceptable salt
Biological result	Inhibition of sterol synthesis
Chemical scope	Markush genus defined by m, n, z, R, and Y variables
Oral administration	Added only by claims 10-14

The absence of a named disease gives claim 1 potentially broad therapeutic reach. The claim is not expressly limited to hypercholesterolemia, dyslipidemia, cardiovascular disease, or a particular biomarker. A patentee would still need to establish that the accused administration meets the “inhibiting sterol synthesis” limitation.

How broad is the formula-I Markush genus?

The formula-I genus includes multiple chain lengths, linker lengths, substituent patterns, and terminal acid or ester groups.

Variable	Claimed range or alternatives	Practical effect
m	Independently 0 to 5	Permits several ring or linker substitution patterns, depending on the displayed formula
n	Independently 3 to 7	Covers multiple hydrocarbon-chain lengths
X	(CH2)z, z = 0 to 4	Allows a direct bond or methylene spacer of varying length
R1, R2, R11, R12	H, C1-C6 alkyl, or phenyl	Broad substitution at four positions
R substituent condition	Not all four may be H	Excludes the fully unsubstituted configuration
Y1, Y2	OH, COOH, or COOR3	Covers acids, alcohols, and ester derivatives
R3	C1-C6 alkyl, phenyl, or benzyl	Expands ester diversity
R3 substitution	Halo, OH, or C1-C6 alkoxy	Adds substituted ester embodiments

The claim therefore covers more than one commercial active ingredient. It reaches a family of substituted aliphatic compounds, including free acids, esters, and salts. The breadth is limited by the precise chemical arrangement shown in formula I, which is absent from the text provided.

The “not all simultaneously H” condition is important. It excludes the unsubstituted parent structure but leaves a large number of mono-, di-, tri-, and tetra-substituted variants.

What do claims 2 through 7 add?

Claims 2 through 7 progressively reduce the chemical scope.

Claim	Narrowing limitation	Commercial or legal significance
2	Y1 and Y2 limited to OH, COOR3, or COOH	Removes any broader Y alternatives not expressly listed
3	m = 0	Selects one core structural arrangement
4	n = 5	Selects one chain-length configuration
5	z = 0	Removes the methylene spacer
6	R1, R2, R11, and R12 are all C1-C6 alkyl	Excludes hydrogen and phenyl at those positions
7	Y1 and Y2 are COOH	Selects the dicarboxylic-acid form

Claim 7 is materially narrower than claim 1 but potentially stronger against validity attacks based on an expansive genus. It defines a fully substituted, dicarboxylic-acid embodiment with m = 0, n = 5, z = 0, and four alkyl substituents.

For bempedoic-acid analysis, claim 7 is particularly relevant because bempedoic acid is a substituted dicarboxylic acid with a long aliphatic chain. Bempedoic acid is chemically identified as 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid. The exact correspondence between the commercial molecule and claim 7 depends on the orientation and atom numbering in the omitted formula-I drawing. The structural images for claims 8 and 9 are also absent from the supplied claim text.

What do claims 8 and 9 protect?

Claims 8 and 9 are species claims that identify particular compounds within the claim-1 genus.

Claim 8 covers one specifically drawn formula-I compound or its pharmaceutically acceptable salt. Claim 9 covers another specifically drawn compound. Because the chemical drawings were not reproduced, the species cannot be named reliably from the textual transcription.

Species claims normally have a narrower infringement surface than the Markush genus, but they can have greater validity resilience when the disclosed compound has demonstrated pharmaceutical activity. If either claim 8 or claim 9 corresponds to bempedoic acid, it would be directly relevant to products containing that active ingredient. If the species are related intermediates, analogues, or alternative sterol-synthesis inhibitors, their commercial relevance would depend on whether those compounds are marketed or used in an approved product.

How do the oral-administration claims affect infringement?

Claims 10 through 14 require oral administration.

Claim	Dependency	Added limitation
10	Claim 1	Oral administration
11	Claim 5	Oral administration
12	Claim 7	Oral administration
13	Claim 8	Oral administration
14	Claim 9	Oral administration

These claims are particularly relevant to oral tablets and capsules. Nexletol and Nexlizet are orally administered products, so an ANDA applicant seeking approval for an oral bempedoic-acid product would face the oral method claims if the listed patent claims the relevant product use.

The oral claims do not require a specific tablet strength, dosing frequency, food condition, formulation excipient, or treatment duration. A generic applicant would therefore need to evaluate whether its proposed labeling and product use practice the claimed method, even if its tablet formulation differs from the branded product.

What is the FDA and Orange Book status?

Bempedoic acid is an FDA-approved small-molecule drug, not a biologic. FDA approved Nexletol in February 2020 and Nexlizet in February 2020. Nexletol contains bempedoic acid. Nexlizet combines bempedoic acid with ezetimibe.[1][2]

The Orange Book is the principal source for determining whether U.S. Patent 9,624,152 is listed against a specific drug product, its use code, and the listed patent expiration information. Patent listing is product-specific. A patent relevant to Nexletol may not automatically be listed against every bempedoic-acid product or combination product.

Representative Orange Book issues include:

Issue	Relevance
Patent listing	Determines whether an ANDA applicant must address the patent through a Paragraph IV certification
Use code	Defines the approved method of use associated with the listed patent
Patent expiration	Establishes the listed date for the relevant patent claim
Pediatric information	May affect regulatory exclusivity, but does not itself extend every patent
Combination product	Nexlizet may involve separate patent and use-code analysis for bempedoic acid and ezetimibe

The FDA Orange Book should control the current listing and expiration analysis. The face of the patent alone does not establish the final Orange Book status.

When does U.S. Patent 9,624,152 lose exclusivity?

The patent issued on April 18, 2017. Its enforceable term depends on the earliest effective nonprovisional or international filing date, patent-term adjustment, terminal disclaimers, and any applicable statutory changes.

For business planning, the relevant distinction is:

• Patent expiration is not the same as FDA regulatory exclusivity.
• Patent-term adjustment can move the expiration date.
• A terminal disclaimer can eliminate an otherwise available term extension.
• Orange Book listing may display a date that should be reconciled against the USPTO patent record.
• A Paragraph IV challenge can create litigation risk before patent expiration.

Patent 9,624,152 is part of the bempedoic-acid patent estate that has been associated with commercial protection into the late 2020s or early 2030s. The precise expiration date should be taken from the current USPTO record and Orange Book entry rather than inferred from the grant date.

What other patents protect bempedoic acid products?

The commercial estate around bempedoic acid is not limited to one method patent. It has included patents directed to compounds, formulations, treatment methods, and combination products.

Patent category	Typical protected subject matter	Risk to a generic applicant
Compound patents	Bempedoic acid and related analogues	Direct active-ingredient coverage
Method-of-use patents	Sterol synthesis inhibition, hyperlipidemia, LDL-C reduction, or cardiovascular-risk reduction	Label and induced-infringement exposure
Formulation patents	Tablets, solid dosage forms, excipient systems, or stability characteristics	Product-design and ANDA exposure
Combination patents	Bempedoic acid plus ezetimibe	Relevant to Nexlizet and fixed-dose combinations
Manufacturing patents	Synthesis, purification, crystallization, or salt formation	API sourcing and supply-chain barriers
Polymorph or salt patents	Solid-state forms and pharmaceutically acceptable salts	Potential API and formulation constraints

Publicly associated U.S. patents in the Esperion bempedoic-acid estate include U.S. Patent Nos. 9,624,152, 10,392,410, and 10,583,110. Their exact claim scope, listing status, and expiration dates differ and must be reviewed patent by patent. The existence of several patents does not mean every patent independently blocks an ANDA. The relevant question is whether at least one unexpired, enforceable claim reads on the proposed product or its labeled use.

What Paragraph IV challenges could arise?

A generic applicant filing an ANDA for bempedoic acid may use one or more of the following certifications:

Certification	Effect
Paragraph I	No patent information is listed
Paragraph II	Listed patent has expired
Paragraph III	Applicant will wait until patent expiration
Paragraph IV	Patent is invalid, unenforceable, or will not be infringed
Section viii statement	Applicant omits a patented method of use from its labeling

For Patent 9,624,152, the central Paragraph IV arguments would likely focus on:

1. Noninfringement based on the proposed labeling or use;
2. Failure of the accused compound to fall within formula I;
3. Failure to meet the sterol-synthesis inhibition limitation;
4. Invalidity for anticipation or obviousness;
5. Written-description or enablement challenges to the breadth of the Markush genus;
6. Indefiniteness of structural or functional limitations;
7. Patent-term or terminal-disclaimer issues.

A Section viii strategy could be available only if the generic label can omit the patented method while still satisfying FDA labeling requirements. That assessment depends on the Orange Book use code and the approved indications.

How strong is the patent estate?

The estate has different strength levels by claim type.

Broad genus claims

Claim 1 has the greatest literal breadth but also the greatest potential exposure to prior-art and written-description challenges. It covers multiple variable ranges and several functional groups. A challenger would likely examine whether the specification supports the full scope of the genus and whether the prior art disclosed overlapping compounds or sterol-synthesis activity.

Narrow subgenus claims

Claims 3 through 7 are narrower and easier to map to a commercial molecule. Claim 7, in particular, may provide a more targeted protection layer around the dicarboxylic-acid embodiment.

Species claims

Claims 8 and 9 can be strong if they cover the marketed active ingredient and the specification demonstrates the claimed activity. Their scope is narrow, but their infringement analysis is more direct.

Oral-use claims

Claims 10 through 14 are commercially relevant for tablet products. They may be less vulnerable to a noninfringement argument when the proposed generic label expressly includes the same oral treatment method.

Overall, the patent estate is stronger as a layered portfolio than as a single broad genus claim. The principal commercial protection comes from the combination of active-ingredient, method-of-use, formulation, and combination-product claims.

What manufacturing and IP barriers affect generic entry?

Generic entry requires more than designing around one patent. A generic applicant must address:

• API identity and stereochemical purity;
• Salt and solid-state form;
• Impurity profile;
• Bioequivalence;
• Stability and degradation products;
• Tablet composition;
• Orange Book-listed method claims;
• Non-listed manufacturing patents;
• Supply agreements and API qualification;
• Potential 30-month stays following Paragraph IV litigation.

Bempedoic acid is a small molecule, so biosimilar approval is not relevant. The applicable pathway is the ANDA pathway under section 505(j) of the Federal Food, Drug, and Cosmetic Act. A 351(k) biosimilar application does not apply.

How does bempedoic acid compare with competing lipid-lowering drugs?

Product	Active ingredient	FDA pathway	Main patent-risk profile
Nexletol	Bempedoic acid	New drug application	Method, compound, formulation, and manufacturing patents
Nexlizet	Bempedoic acid plus ezetimibe	New drug application	Combination-product claims plus separate ezetimibe issues
Repatha	Evolocumab	Biologics license application	Biosimilar and biologic patent litigation
Praluent	Alirocumab	Biologics license application	Biosimilar and antibody patent issues
Crestor generics	Rosuvastatin	ANDA	Small-molecule compound, formulation, and use patents
Zetia generics	Ezetimibe	ANDA	Small-molecule and combination-product issues

Bempedoic acid faces generic-drug risk rather than biosimilar risk. Its commercial differentiation is based on mechanism, oral administration, and use in patients who require additional LDL-C lowering or cannot adequately use statin therapy. Patent exposure therefore centers on ANDA timing and method-of-use litigation.

What licensing deals affect the patent landscape?

Esperion has entered commercialization arrangements for bempedoic-acid products outside the United States, including agreements involving Daiichi Sankyo in certain territories. These arrangements can affect regional commercialization, supply, and enforcement rights, but they do not by themselves determine U.S. patent ownership or Orange Book listing.

Geographic analysis should separate:

• U.S. patent ownership and enforcement;
• European and other national patent families;
• Regional marketing rights;
• Local regulatory approvals;
• Local SPC or patent-term-extension rights;
• Territory-specific settlement or license restrictions.

A licensee’s ability to commercialize a product in Europe does not establish freedom to operate in the United States.

What generic launch scenarios exist?

Three principal launch scenarios are relevant.

Launch after patent expiration

The applicant waits for the relevant listed patents to expire. This reduces litigation risk but delays entry and may allow multiple competitors to prepare simultaneously.

Paragraph IV launch

The applicant challenges validity, enforceability, or infringement. The first filer may seek 180-day exclusivity if statutory requirements are met. Litigation can trigger a 30-month stay of FDA approval, subject to statutory exceptions.

Label carve-out

The applicant removes a patented use from its labeling. This strategy is viable only when the remaining label supports approval and the carved-out use is not required for the product’s approved marketing.

For a broad oral bempedoic-acid product, the highest-risk scenario is a Paragraph IV filing that retains the same sterol-synthesis or lipid-lowering language associated with the listed patent.

Key Takeaways

• U.S. Patent 9,624,152 is primarily a method-of-use patent, not a standalone composition patent.
• Claim 1 covers administration of a broad formula-I genus to inhibit sterol synthesis.
• Claims 3 through 7 narrow the genus toward a substituted dicarboxylic-acid structure relevant to bempedoic acid.
• Claims 10 through 14 directly target oral products.
• Claims 8 and 9 are species claims, but their compounds cannot be identified from the supplied text because the structural drawings are missing.
• Bempedoic acid is a small molecule and faces ANDA, not biosimilar, competition.
• The commercial patent estate includes compound, method, formulation, combination, and manufacturing protections.
• Orange Book use codes and current patent listings control the practical Paragraph IV analysis.
• The strongest generic defenses are likely to involve claim construction, structural noninfringement, label carve-outs, written description, enablement, obviousness, and patent-term analysis.
• Nexletol and Nexlizet create separate product-specific listing and combination-product issues.

FAQs About U.S. Patent 9,624,152

Is U.S. Patent 9,624,152 a bempedoic acid composition patent?

No. The supplied claims are directed to methods of administering a pharmaceutical composition containing a formula-I compound. They do not independently claim bempedoic acid as a composition of matter.

Does Patent 9,624,152 cover Nexletol?

It may cover Nexletol if the patent is listed for the product and the product’s labeled oral use practices the asserted claims. The current Orange Book entry and use code control the regulatory analysis.

Can a generic bempedoic-acid applicant avoid this patent by changing excipients?

Not necessarily. Claims 1 through 14 focus primarily on the active compound, treatment method, and oral administration. A different excipient system may avoid a formulation claim but may not avoid a method claim.

Are biosimilars relevant to bempedoic acid?

No. Bempedoic acid is a chemically synthesized small molecule. Generic competition proceeds through the ANDA pathway rather than the biosimilar pathway.

What is the most important claim for an oral bempedoic-acid product?

The answer depends on the formula-I mapping and Orange Book listing, but claims 7, 12, 13, and 14 are commercially important because they combine narrower chemical embodiments or identified species with oral administration.

References

1. U.S. Food and Drug Administration. (2020). Nexletol (bempedoic acid) prescribing information.
2. U.S. Food and Drug Administration. (2020). Nexlizet (bempedoic acid and ezetimibe) prescribing information.
3. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations, Orange Book.
4. United States Patent and Trademark Office. (2017). U.S. Patent No. 9,624,152, methods of inhibiting sterol synthesis.
5. Esperion Therapeutics, Inc. (2024). Annual report on Form 10-K.
6. United States Code, 21 U.S.C. § 355.

Drugs Protected by US Patent 9,624,152

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate

International Family Members for US Patent 9,624,152

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	2404890		301062	Netherlands
European Patent Office	2404890		LUC00174	Luxembourg
European Patent Office	2404890		122020000048	Germany
European Patent Office	2404890		132020000000112	Italy
European Patent Office	2404890		2020C/534	Belgium
European Patent Office	2404890		CA 2020 00041	Denmark