U.S. Patent 7,932,268: Lomitapide Titration Regimen, Claim Scope, Expiration, and Patent Landscape
U.S. Patent No. 7,932,268 protects a stepwise dose-escalation method for treating hyperlipidemia or hypercholesterolemia with lomitapide, an microsomal triglyceride transfer protein inhibitor. The patent does not primarily protect lomitapide as a chemical compound. Its enforceable value is concentrated in the claimed titration sequence, treatment duration, patient population, oral administration, and specified lipid-reduction outcomes.
The patent’s nominal expiration date is June 1, 2025, based on the patent’s earliest effective U.S. priority date. The central claim is a method-of-use claim. A generic or alternative product would not necessarily infringe merely by containing lomitapide. Infringement depends on whether the accused party induces or performs the claimed multi-stage dosing regimen.
What does U.S. Patent 7,932,268 cover?
U.S. Patent 7,932,268 covers treatment of hyperlipidemia or hypercholesterolemia by administering lomitapide through at least three progressively higher daily dose levels.
The independent claim requires all of the following:
| Claim element |
Requirement |
| Patient |
A subject suffering from hyperlipidemia or hypercholesterolemia |
| Active agent |
An MTP inhibitor having the claimed lomitapide structure, a pharmaceutically acceptable salt, or the piperidine N-oxide |
| Dosing format |
At least three stepwise, increasing dose levels |
| First dose |
About 2 to about 13 mg/day |
| Second dose |
About 5 to about 30 mg/day |
| Third dose |
About 10 to about 50 mg/day |
| Duration |
Each dose level administered for about 1 to 4 weeks |
| Treatment objective |
Administration of an effective amount |
The patent is therefore directed to controlled escalation rather than a fixed-dose lomitapide regimen.
What molecule is identified by the claimed structure?
The claimed compound is lomitapide, also known as BMS-201038 and by the chemical name lomitapide mesylate when formulated as its mesylate salt. Lomitapide inhibits microsomal triglyceride transfer protein, or MTP, reducing the assembly and secretion of apolipoprotein B-containing lipoproteins.
The claim also covers:
- Pharmaceutically acceptable salts of the claimed MTP inhibitor.
- The piperidine N-oxide form.
- Oral administration under dependent claim 5.
- Treatment of severe hypercholesterolemia under dependent claim 2.
The structure is important because the claim is not written broadly to cover every MTP inhibitor. A different MTP inhibitor would fall outside the literal chemical limitation unless the patent’s construction or equivalents analysis supported a broader interpretation.
How does the independent claim work?
Claim 1 combines a chemical limitation with a sequential treatment protocol.
The dose ranges overlap substantially:
- First dose: 2-13 mg/day
- Second dose: 5-30 mg/day
- Third dose: 10-50 mg/day
A compliant regimen might use:
| Stage |
Example dose |
Required duration |
| First stage |
5 mg/day |
1-4 weeks |
| Second stage |
10 mg/day |
1-4 weeks |
| Third stage |
20 mg/day |
1-4 weeks |
The claim does not require a specific dose selected from the full range. It requires a sequence in which each later dose is higher than the preceding dose and each stage lasts approximately one to four weeks.
The phrase “about” creates potential claim-construction disputes. Courts generally interpret “about” in light of the specification, prosecution history, technical context, and evidence of how a skilled person would understand the range. It does not automatically permit unlimited variation.
Does the claim require every dose stage to fall within a different range?
Yes. For literal infringement, the first, second, and third dose levels must correspond to the respective claimed ranges. A regimen using 10 mg/day, 20 mg/day, and 40 mg/day would generally fit the three principal ranges, assuming the administration periods and other limitations are met.
The claim also requires increasing dose levels. A regimen of 10 mg/day, 10 mg/day, and 20 mg/day would present a non-increasing middle stage and create a potential noninfringement position.
What do claims 2 through 8 add?
The dependent claims narrow the scope of claim 1.
| Claim |
Added limitation |
Commercial significance |
| 2 |
Severe hypercholesterolemia |
Targets the homozygous familial hypercholesterolemia, or HoFH, population more directly |
| 3 |
At least 15% reduction in one or more specified lipid parameters |
Adds an efficacy threshold |
| 4 |
At least 25% reduction in one or more specified lipid parameters |
Narrower efficacy limitation |
| 5 |
Oral administration |
Aligns the claim with the marketed oral product |
| 6 |
A fourth dose level |
Requires escalation beyond the first three stages |
| 7 |
Fourth and fifth dose levels |
Requires a five-stage escalation sequence |
| 8 |
Fourth dose of 20-60 mg/day and fifth dose of 30-75 mg/day |
Defines higher-dose escalation stages |
The lipid parameters include total cholesterol, LDL cholesterol, fasting triglycerides, VLDL, lipoprotein(a), and apolipoprotein B. The text supplied for claims 3 and 4 contains a typographical artifact before “lipoprotein B”; the intended limitation is generally understood to be apolipoprotein B.
How broad are claims 6 through 8?
Claims 6 through 8 cover extended titration schedules. Claim 8 is the most specific:
- Fourth stage: about 20-60 mg/day
- Fifth stage: about 30-75 mg/day
A five-stage regimen of 5, 10, 20, 40, and 60 mg/day could potentially fall within claim 8, assuming each dose is administered for the required one-to-four-week period and all other claim 1 elements are satisfied.
The upper dose range in claim 8 is broader than the dose commonly associated with the approved starting and maintenance instructions for Juxtapid. That does not make the claim automatically invalid, but it raises enablement, written-description, anticipation, obviousness, and regulatory-use questions depending on the evidence in the patent record.
What is the patent’s legal status and expiration date?
| Item |
Data |
| Patent |
U.S. 7,932,268 |
| Title |
Methods for treating hyperlipidemia |
| Patent type |
Utility patent |
| Core subject matter |
Stepwise lomitapide dose escalation |
| Grant date |
April 26, 2011 |
| Earliest priority date |
June 1, 2005 |
| Nominal patent expiration |
June 1, 2025 |
| Patent term adjustment or extension |
Must be confirmed from the USPTO patent record and Orange Book entry |
| Regulatory product associated with the method |
Juxtapid, lomitapide |
| FDA approval holder at approval |
Aegerion Pharmaceuticals |
The patent’s nominal term is calculated from the earliest effective nonprovisional priority date under the applicable patent-term rules. Any patent-term adjustment or patent-term extension could alter the operative expiration date. The controlling dates are the USPTO patent record and the FDA Orange Book listing, not the grant date.
Because the claims are method claims, expiration eliminates the patent-based restriction on practicing the claimed regimen in the United States. It does not, by itself, eliminate other patents covering lomitapide, its formulations, manufacturing processes, or separate methods of treatment.
What is the Orange Book status of U.S. Patent 7,932,268?
U.S. Patent 7,932,268 has been associated with Juxtapid as a method-of-use patent. The listing is significant because an ANDA applicant seeking approval for lomitapide may have to address the patent through a Paragraph IV certification, a statement that the patent is not infringed, is invalid, or is unenforceable, or a section viii statement carving out the patented use.
The key distinction is between:
- Product approval: approval to market the active ingredient and dosage form.
- Method-of-use protection: protection for practicing the patented titration regimen.
- Label content: the extent to which the proposed generic label instructs the patented method.
Under the Hatch-Waxman framework, an ANDA applicant can sometimes avoid infringement exposure by omitting a patented indication or dosing instruction from its proposed labeling. This strategy is commonly referred to as a section viii carve-out. Its effectiveness depends on the wording of the proposed label, the patent claims, the reference product label, promotional conduct, and inducement evidence. [4]
When does U.S. Patent 7,932,268 lose exclusivity?
The nominal expiration date is June 1, 2025. If no effective patent-term adjustment or extension changes that date, the patent no longer blocks practice of its claimed regimen after that date.
The relevant exclusivity timeline is:
| Event |
Date or period |
| Earliest claimed priority |
June 1, 2005 |
| Patent grant |
April 26, 2011 |
| Juxtapid FDA approval |
December 21, 2012 |
| New chemical entity exclusivity |
Through December 21, 2017 |
| Nominal patent expiration |
June 1, 2025 |
NCE exclusivity and patent exclusivity are separate. NCE exclusivity prevented FDA approval of an ANDA or 505(b)(2) application relying on the reference drug for five years, subject to the statutory framework. It did not extend the patent term.
What infringement conduct would fall within the claims?
Potentially infringing conduct would require a regimen that satisfies the claim limitations. Examples include:
- Marketing a lomitapide product with instructions to begin at a dose within 2-13 mg/day.
- Directing patients to escalate to a dose within 5-30 mg/day.
- Directing a further increase to a dose within 10-50 mg/day.
- Maintaining each stage for approximately one to four weeks.
- Promoting the regimen for hyperlipidemia or hypercholesterolemia.
A manufacturer could face induced-infringement allegations if its labeling or promotional materials actively encouraged the patented regimen. A physician’s administration of the regimen could raise direct-infringement issues, although practical enforcement against physicians would be commercially and legally distinct from enforcement against a drug manufacturer.
What conduct may avoid literal infringement?
Potential noninfringement positions include:
- Using a different active compound that is not the claimed lomitapide structure or a covered salt or N-oxide.
- Using a fixed dose without stepwise escalation.
- Using fewer than three dose stages.
- Using stage durations outside the claimed one-to-four-week periods, subject to interpretation of “about.”
- Omitting instructions that encourage the patented regimen.
- Using a dose sequence that does not increase at every stage.
- Selling for a nonclaimed use with a legally effective label carve-out.
These positions do not eliminate potential liability under the doctrine of equivalents or induced infringement. They also do not address separate patents.
How strong is the patent estate for lomitapide?
The strength of U.S. 7,932,268 depends on the type of challenge.
Infringement strength
The patent has meaningful infringement leverage where a competitor’s labeling reproduces the approved lomitapide titration protocol. The claim is narrower than a compound claim but may map closely onto the clinical dosing instructions for the marketed product.
Its strongest feature is the combination of:
- The specific active ingredient.
- Stepwise escalation.
- Dose ranges corresponding to clinical titration.
- Defined duration for each stage.
- Hyperlipidemia or hypercholesterolemia treatment.
Its weakness is that a competitor may be able to avoid infringement by altering label language, using a different titration pattern, or relying on a skinny-label strategy.
Validity strength
Potential validity vulnerabilities include:
- Anticipation: Earlier publications or patent documents may disclose lomitapide treatment using the claimed sequence.
- Obviousness: A challenger could argue that gradual dose escalation was an expected clinical approach for an MTP inhibitor with tolerability concerns.
- Written description: The patent must adequately support the full breadth of each dose range, duration range, and optional fourth and fifth stages.
- Enablement: The specification must enable the claimed regimen across its full scope without undue experimentation.
- Indefiniteness: Terms such as “about,” “effective amount,” and “step-wise, increasing” may be litigated, although these terms are common in pharmaceutical patents.
- Double patenting: Related continuation or divisional patents may create obviousness-type double-patenting issues.
The patent’s validity cannot be determined from the claim text alone. The specification, prosecution history, cited prior art, examiner amendments, and any post-grant or district-court record control the analysis.
What formulation patents protect lomitapide?
U.S. 7,932,268 is not principally a formulation patent. It does not claim a tablet composition, excipient system, dissolution profile, particle-size distribution, or specific solid-state form as the central inventive concept.
Separate formulation or composition patents could cover:
- Lomitapide mesylate tablets.
- Specific excipient combinations.
- Immediate-release oral dosage forms.
- Stability-enhanced formulations.
- Salt forms or solid-state forms.
- Packaging or storage conditions.
- Manufacturing processes for the active ingredient or dosage form.
Those rights must be analyzed separately from the titration patent. A product may avoid U.S. 7,932,268 yet still encounter formulation or manufacturing patents. Conversely, expiration of the titration patent does not establish freedom to operate for every lomitapide product.
Are biosimilar risks relevant to lomitapide?
No. Lomitapide is a chemically synthesized small molecule, not a biologic. The relevant competitive pathway is an ANDA under section 505(j) of the Federal Food, Drug, and Cosmetic Act, or potentially a 505(b)(2) application for a product relying partly on published or listed data.
The principal regulatory risks are therefore:
- Paragraph IV patent challenges.
- Label carve-outs.
- Formulation and manufacturing patents.
- Bioequivalence.
- Product quality and chemistry, manufacturing, and controls requirements.
- Risk Evaluation and Mitigation Strategy obligations, if applicable to the reference product or proposed product.
Biosimilar approval under the Public Health Service Act is not the applicable pathway.
Which companies could challenge or compete with Juxtapid?
The commercial field includes:
| Company or product |
Role |
| Aegerion Pharmaceuticals |
Original U.S. sponsor of Juxtapid |
| Amryt Pharma |
Later commercial owner associated with the Juxtapid business |
| Generic ANDA sponsors |
Potential competitors through 505(j) applications |
| Statin manufacturers |
Indirect competitors in broader lipid management |
| PCSK9 inhibitor manufacturers |
Competitive alternatives for severe hypercholesterolemia |
| ANGPTL3 inhibitor developers |
Emerging alternatives for refractory lipid disorders |
| Lipoprotein apheresis providers |
Non-drug alternative for selected HoFH patients |
The narrow indication and safety-monitoring burden reduce the practical value of a label-only generic launch unless the product can satisfy regulatory requirements and obtain commercial access through specialty distribution and payer channels.
What generic launch scenarios exist?
Scenario 1: Full-label ANDA launch
A generic applicant includes the patented titration regimen in its proposed labeling. This creates the clearest infringement exposure if the patent remains enforceable and listed.
Scenario 2: Section viii carve-out
The applicant omits the patented method from labeling while retaining nonpatented uses. This can permit earlier approval, but the carve-out must be consistent with the actual label and promotional conduct.
Scenario 3: Paragraph IV challenge
The applicant certifies that the patent is invalid, unenforceable, or not infringed. A timely patent-infringement lawsuit can trigger the statutory 30-month stay under the Hatch-Waxman framework. [4]
Scenario 4: Post-expiration launch
After patent expiration, the method-of-use barrier falls away, subject to any other unexpired Orange Book-listed patents, regulatory exclusivity, and product-specific approval requirements.
Scenario 5: Alternative regimen
A competitor markets a regimen outside the claimed dose sequence or duration. This approach may reduce literal infringement risk but may create clinical, labeling, or physician-adoption disadvantages.
What patent litigation affects U.S. Patent 7,932,268?
The patent number alone does not establish whether a current Paragraph IV dispute, ANDA litigation case, settlement agreement, or license remains active. Those matters must be determined from the FDA Orange Book, FDA patent-certification records where available, district-court dockets, appellate decisions, and SEC filings.
For transaction diligence, the relevant records are:
- USPTO Patent Center for prosecution history and term data.
- FDA Orange Book for current listing and expiration information.
- Federal district-court dockets for Hatch-Waxman litigation.
- Federal Circuit opinions for claim construction and validity rulings.
- Aegerion, Amryt, or successor-company filings for licenses and settlements.
- ANDA litigation databases and Paragraph IV notices.
The claim text does not itself disclose a license, settlement, covenant not to sue, or authorized-generic arrangement.
Does U.S. 7,932,268 protect the marketed Juxtapid dose?
It likely overlaps materially with the clinical titration concept used for Juxtapid because the patent claims escalation from low initial doses toward higher daily doses. The overlap is strongest where the product labeling instructs weekly or multiweek escalation through the claimed ranges.
The patent does not necessarily cover every use of Juxtapid. A fixed-dose prescription, a nonescalating regimen, or an off-label dose sequence may not satisfy all claim limitations. Patent scope is determined claim by claim, not by the general fact that the product contains lomitapide.
Key Takeaways
- U.S. Patent 7,932,268 is a method-of-treatment patent directed to stepwise lomitapide dose escalation.
- Claim 1 requires at least three increasing dose stages, specific overlapping daily-dose ranges, and one to four weeks at each stage.
- The patent covers lomitapide, its pharmaceutically acceptable salts, and the piperidine N-oxide form identified in the claim.
- Claims 2 through 8 narrow the invention to severe hypercholesterolemia, oral administration, lipid-reduction thresholds, and four- or five-stage escalation.
- The patent is not principally a composition, formulation, or manufacturing patent.
- The nominal expiration date is June 1, 2025, subject to confirmation of any patent-term adjustment or extension.
- Lomitapide is a small molecule, so biosimilar law does not apply.
- Generic competition would likely proceed through an ANDA, Paragraph IV certification, section viii carve-out, or post-expiration launch.
- The principal commercial vulnerability is that the method claims may be designed around through label drafting or an alternative titration sequence.
- Separate lomitapide composition, formulation, process, and method-of-use patents must be reviewed before concluding freedom to operate.
Frequently Asked Questions
Does U.S. Patent 7,932,268 cover all lomitapide products?
No. It covers specified treatment regimens using the claimed MTP inhibitor. A product can contain lomitapide without practicing every limitation of the claims.
Can a generic omit the patented lomitapide titration regimen?
Potentially. A section viii label carve-out may avoid approval for a patented method, but the proposed labeling and promotional conduct must not instruct or encourage the carved-out use.
Is a 5 mg to 10 mg to 20 mg lomitapide regimen covered?
It may be. The sequence falls within the principal dose ranges, but infringement also requires the claimed treatment indication and approximately one to four weeks at each dose level.
Does expiration of U.S. 7,932,268 permit immediate generic launch?
Not necessarily. Other unexpired patents, regulatory exclusivity, approval requirements, litigation orders, or separate formulation and manufacturing rights may remain relevant.
Is lomitapide subject to biosimilar competition?
No. Lomitapide is a small-molecule drug. Competition would generally use the ANDA or 505(b)(2) pathway rather than the biosimilar pathway.
References
- United States Patent and Trademark Office. (2011). U.S. Patent No. 7,932,268, Methods for treating hyperlipidemia.
- U.S. Food and Drug Administration. (2012). Juxtapid (lomitapide mesylate) prescribing information.
- U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations (Orange Book).
- Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 355(j).
- Code of Federal Regulations. (2024). 21 C.F.R. § 314.94, Content and format of an abbreviated new drug application.
