US Patent 10,337,003: Eteplirsen Patent Scope, Exondys 51 Exclusivity, and DMD Patent Landscape

US Patent 10,337,003 protects a specific clinical-use regimen for eteplirsen in Duchenne muscular dystrophy, rather than eteplirsen as a chemical compound. Its core limitations are exon 51-amenable DMD, a 30-50 mg/kg dose, phosphate-buffered saline, treatment long enough to increase dystrophin-positive muscle fibers to at least 20% of normal, and, in dependent claims, weekly infusion, steroid pretreatment, and pediatric male patients. The patent is materially relevant to Exondys 51 generic-entry analysis, but it does not by itself block every possible eteplirsen product or every noninfringing dosing regimen.

What does US Patent 10,337,003 protect?

US Patent 10,337,003 is a method-of-treatment patent assigned to Sarepta Therapeutics covering eteplirsen treatment for DMD patients whose mutations are amenable to exon 51 skipping.[1]

The independent claim requires all of the following:

Limitation	Claim requirement
Disease	Duchenne muscular dystrophy
Patient	Human subject
Genetic status	DMD mutation amenable to exon 51 skipping
Active agent	Eteplirsen
Vehicle	Phosphate-buffered saline
Dose	About 30 mg/kg to about 50 mg/kg
Treatment duration	Long enough to achieve the specified biological result
Biomarker result	At least 20% of normal dystrophin-positive fibers

The claim is not a broad claim to all exon-skipping therapy. It is also not a pure composition claim. A competitor generally would need to practice the claimed administration method, or induce its practice, to create direct method-infringement exposure.

What is the commercial subject of the patent?

The patent is closely aligned with Exondys 51, the FDA-approved eteplirsen product. Exondys 51 is a phosphorodiamidate morpholino oligomer, or PMO, designed to skip exon 51 of the DMD gene. FDA approved Exondys 51 under the accelerated-approval pathway on September 19, 2016, for patients with a confirmed mutation amenable to exon 51 skipping.[2]

The approved label recommends 30 mg/kg administered once weekly by intravenous infusion.[3] That approved regimen falls directly within the principal dosing range in claim 1 and within the specific 30 mg/kg limitation in claim 3.

How do the 12 claims differ?

Claims 1 through 12 form a nested set of treatment limitations. Claims 2 through 12 narrow claim 1 and do not stand independently.

Claim	Additional limitation	Scope significance
1	Eteplirsen, PBS, 30-50 mg/kg, exon 51-amenable DMD, at least 20% dystrophin-positive fibers	Broadest claim
2	Dystrophin-positive fibers increase to about 50% of normal	Higher biological-response threshold
3	Dose is about 30 mg/kg	Tracks the approved Exondys 51 dose
4	Systemic administration	Excludes purely local administration
5	Once-weekly infusion	Closely tracks the FDA-labeled regimen
6	Concomitant steroid administration	Requires steroid use
7	Stable steroid dose for at least 24 weeks before first eteplirsen dose	Adds a pretreatment requirement
8	Steroid is a glucocorticoid	Narrows claim 7
9	Patient is 7 to 13 years old	Pediatric age limitation
10	Patient is a boy, in the 7-13 age group	Pediatric male limitation
11	Steroid-stabilized patient is 7 to 13 years old	Combines claims 7 and 9
12	Steroid-stabilized patient is a boy aged 7 to 13	Narrowest express patient profile

Claim 1 is the principal enforcement claim. Claims 3 and 5 are commercially important because they track the labeled 30 mg/kg weekly infusion regimen. Claims 7 through 12 are narrower and depend on clinical facts that may be difficult to establish across an entire patient population.

What is the infringement scope of claim 1?

Claim 1 requires a treatment course that produces at least 20% of normal dystrophin-positive fibers. This is a functional treatment-result limitation. A claimant would likely need evidence that the accused treatment produced, or was intended to produce, the claimed dystrophin result.

The claim also contains several potentially contested terms:

“About 30 mg/kg to about 50 mg/kg”
“Amenable to exon 51 skipping”
“A period of time sufficient”
“At least 20% of normal”
“Dystrophin-positive fibers”
“Phosphate-buffered saline”

The use of “about” creates a range-boundary issue. A dose slightly below 30 mg/kg or above 50 mg/kg could still raise infringement questions depending on claim construction, prosecution history, and evidence concerning clinical equivalence.

“Amenable to exon 51 skipping” limits the patent to genetically defined DMD patients. Patients with mutations requiring exon 45, 53, or other exon skipping are outside the literal scope of claim 1.

The composition limitation also matters. Claim 1 identifies a composition comprising eteplirsen and phosphate-buffered saline. A formulation using another vehicle could create a noninfringement argument, although that argument would depend on the meaning of “comprising,” the actual formulation, and the patent’s specification.

Which claims most closely track the Exondys 51 label?

Claims 3, 4, and 5 have the strongest direct overlap with the approved Exondys 51 regimen.

FDA-labeled Exondys 51 feature	Corresponding patent claim
Eteplirsen	Claim 1
DMD mutation amenable to exon 51 skipping	Claim 1
30 mg/kg dose	Claim 3
Intravenous infusion	Claim 4
Once-weekly administration	Claim 5
Pediatric DMD population	Claims 9-12, subject to age and steroid requirements

The label does not necessarily require every limitation in claims 6 through 12. In particular, a stable glucocorticoid dose for at least 24 weeks before eteplirsen treatment is a narrower requirement than the general FDA indication.

When does US Patent 10,337,003 expire?

The patent has a 20-year term measured from the relevant earliest nonprovisional filing date, subject to patent-term adjustment, terminal disclaimers, and any applicable patent-term extension.

The family claims priority to a 2011 filing, while the relevant nonprovisional or international filing date is generally identified as June 15, 2012. On that basis, the nominal term is expected to run to approximately June 15, 2032, before any patent-term adjustment.[1]

Exclusivity category	Date or period
Patent grant	July 2, 2019
Nominal patent-term endpoint	Approximately June 15, 2032
FDA approval of Exondys 51	September 19, 2016
Orphan-drug exclusivity	Seven years from approval, through approximately September 19, 2023
Regulatory exclusivity after September 2023	No orphan exclusivity remaining
Patent protection after September 2023	Potentially continues through the patent term, subject to legal status and term adjustments

The exact expiration date should be taken from the USPTO patent-term calculation rather than inferred solely from the 20-year rule. FDA regulatory exclusivity and patent exclusivity are separate rights. The expiration of orphan exclusivity did not terminate US Patent 10,337,003.

What is the Orange Book status of Exondys 51?

Exondys 51 is listed in FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations, commonly called the Orange Book, under NDA 206488.[4]

Orange Book listing is significant because a generic applicant may need to make one or more certifications concerning listed patents:

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.

For a method-of-use patent, an applicant may use a section viii statement and carve out the patented use if the remaining labeling supports approval without the protected indication. That option depends on how the listed patent claims correspond to the approved use and whether the protected method can be removed from labeling.

A Paragraph IV certification against US Patent 10,337,003 would create litigation risk if the patent is listed and the certification is properly notified to the patent owner. A paragraph IV notice generally gives the NDA holder an opportunity to file suit within 45 days, which can trigger a statutory stay of approval for up to 30 months under the Hatch-Waxman framework.[5]

Are there known Paragraph IV challenges to eteplirsen?

No publicly established Paragraph IV litigation against US Patent 10,337,003 is identified in the patent and FDA materials cited here. The absence of a reported case does not establish that no certification has been filed, because certifications and commercial generic-development activity may not be fully visible before litigation or FDA approval.

The principal legal risk would arise from an ANDA applicant seeking approval for an eteplirsen product that uses:

The 30 mg/kg dose;
Once-weekly infusion;
Exon 51-skipping labeling;
A PBS-based formulation; and
Labeling or instructions consistent with the claimed dystrophin response.

A generic applicant could instead pursue one or more design-around positions:

Use a dose outside the claimed range;
Seek a carve-out from the patented use;
Use a different formulation vehicle;
Challenge the written description or enablement of the dystrophin threshold;
Challenge the definiteness of “about,” “normal,” or “sufficient”; or
Argue that the claimed result is not an inherent consequence of the proposed product and regimen.

What other patents cover eteplirsen and Exondys 51?

The Exondys 51 patent estate is broader than US Patent 10,337,003. Relevant categories include:

Patent category	Typical protected subject matter	Competitive significance
PMO chemistry	Phosphorodiamidate morpholino oligomers and related structures	Can restrict active-agent substitution
Exon-skipping sequences	Oligomer sequences directed to DMD exon 51	May cover the specific eteplirsen sequence
Formulation	Aqueous formulations, buffers, concentration, stability, and administration	Can complicate formulation design-arounds
Manufacturing	Oligomer synthesis, purification, scale-up, and quality attributes	May create supply-chain or process barriers
Treatment methods	Dose, frequency, patient selection, and dystrophin response	Directly relevant to clinical-use infringement
Regulatory listing	FDA-listed patents associated with NDA 206488	Determines Hatch-Waxman certification exposure

US Patent 10,337,003 should therefore be analyzed as one layer of the estate. It does not establish freedom to operate for an alternative eteplirsen composition, manufacturing process, or exon-51 oligonucleotide sequence.

How does eteplirsen compare with competing exon-skipping drugs?

Eteplirsen is one of several exon-skipping products developed for genetically defined DMD subgroups.

Product	Active agent	Target exon	Sponsor or manufacturer	FDA status
Exondys 51	Eteplirsen	51	Sarepta Therapeutics	Approved in 2016
Vyondys 53	Golodirsen	53	Sarepta Therapeutics	Approved in 2019
Viltepso	Viltolarsen	53	NS Pharma	Approved in 2020
Amondys 45	Casimersen	45	Sarepta Therapeutics	Approved in 2021
Elevidys	Delandistrogene moxeparvovec	Micro-dystrophin gene therapy	Sarepta Therapeutics	Approved in 2023, with later label expansion

Golodirsen, viltolarsen, and casimersen generally fall outside the literal scope of the eteplirsen claims because they target different exons and use different active agents. Their patent estates remain relevant for the broader DMD market but do not ordinarily provide a direct substitute for an exon 51 product.

Does biosimilar law apply to eteplirsen?

No. Eteplirsen is a synthetic antisense PMO, not a biologic administered through the biosimilar pathway. A competing product would generally be evaluated under the small-molecule or complex-drug framework, most plausibly an ANDA or, depending on product differences, a 505(b)(2) application.

The absence of a biosimilar pathway does not eliminate regulatory barriers. A competing applicant would still need to address:

Active-ingredient sameness;
Oligomer sequence and molecular characterization;
Purity and impurity profile;
Pharmacokinetic comparability;
Immunogenicity and safety;
Manufacturing consistency;
Formulation and container compatibility; and
Any listed patents and exclusivity.

What manufacturing and intellectual-property barriers affect generic entry?

PMO products can present greater characterization and manufacturing complexity than conventional small-molecule tablets. Relevant barriers include oligomer length distribution, sequence-related impurities, depurination or degradation products, aggregation, purification, analytical comparability, and control of injectable-product attributes.

A successful patent challenge to US Patent 10,337,003 would not necessarily clear the entire Exondys 51 estate. A generic or follow-on applicant would need a claim-by-claim freedom-to-operate analysis covering composition, sequence, formulation, manufacturing, and use patents.

What is the commercial exposure from Exondys 51?

Exondys 51 is a targeted product for a genetically defined subgroup of DMD patients. Its revenue exposure is concentrated rather than broad-based. The commercial risk from patent loss depends on:

The number of US patients with exon 51-amenable mutations;
Continued treatment duration;
The number of approved or marketable competing products;
The timing of an ANDA approval;
Whether a challenger launches at risk;
Whether a settlement creates a licensed entry date; and
Whether payers favor a lower-priced generic or follow-on product.

Because Exondys 51 is an orphan product, even a single approved competitor could exert substantial pricing pressure. A generic launch would not require a biosimilar interchangeability determination, but substitution mechanics could differ depending on the FDA pathway and product designation.

What is the patent strength of US Patent 10,337,003?

The patent has meaningful commercial relevance because its principal claim tracks the FDA-approved 30 mg/kg weekly treatment regimen. Its main vulnerabilities are claim construction and proof of the biological-result limitation.

Strength	Risk
Tracks approved exon 51 indication	“Amenable to exon 51 skipping” may require genetic classification evidence
Covers 30 mg/kg dose	“About” creates boundary disputes
Covers weekly infusion through claim 5	Label carve-out may be possible
Includes dystrophin-response threshold	Biological-result proof may be complex
Patent term potentially extends to 2032	Exact term depends on USPTO adjustment and disclaimers
Applies to method of treatment	Does not automatically cover every eteplirsen product

The patent is strongest against a product labeled and administered exactly as Exondys 51. It is weaker against a product using a materially different dose, vehicle, frequency, or labeling strategy, although other patents may close those design-around routes.

Key Takeaways

US Patent 10,337,003 is a method-of-treatment patent for eteplirsen in exon 51-amenable DMD.
Claim 1 covers 30-50 mg/kg, PBS, a human DMD patient, and a dystrophin-positive fiber response of at least 20% of normal.
Claims 3 and 5 closely track the Exondys 51 label: 30 mg/kg once weekly by infusion.
Claims 6 through 12 add steroid pretreatment, glucocorticoid use, pediatric age, and male-patient limitations.
The nominal patent term is expected to extend to approximately June 15, 2032, subject to USPTO term calculations.
Exondys 51’s seven-year orphan exclusivity expired in approximately September 2023; patent protection is separate.
No publicly established Paragraph IV litigation against this patent is identified in the cited materials.
Eteplirsen is not subject to the biosimilar pathway.
Generic-entry analysis must include composition, sequence, formulation, manufacturing, and other method patents beyond US 10,337,003.

FAQs

Can a competitor avoid US Patent 10,337,003 by using less than 30 mg/kg?

Potentially, but the result depends on claim construction of “about 30 mg/kg” and the complete patent record. A dose materially below the claimed range presents a stronger noninfringement position than a marginally lower dose.

Does the patent cover eteplirsen administered to adults?

Claim 1 is not limited to a specific age. Claims 9 through 12 add the 7-to-13-year-old limitation. An adult regimen could therefore fall within claim 1 if all of its other limitations are met.

Does claim 1 require steroid pretreatment?

No. Steroid administration is introduced in claim 6. The 24-week stable-dose requirement appears in claim 7 and applies to the claims that depend on it.

Can an ANDA applicant remove exon 51 use from its label?

A section viii carve-out may be available for a patented method of use, but the remaining label must support approval without encouraging or requiring the protected use. The feasibility depends on the listed patent claims, FDA labeling, and the proposed product’s indication.

Does a patent challenge to US 10,337,003 eliminate all Exondys 51 patent risk?

No. The patent is one component of the broader estate. A challenger would also need to assess patents covering eteplirsen’s PMO sequence, composition, formulation, manufacturing process, and other treatment methods.

References

United States Patent and Trademark Office. (2019). U.S. Patent No. 10,337,003, methods of treating Duchenne muscular dystrophy.
U.S. Food and Drug Administration. (2016). FDA grants accelerated approval to first drug for Duchenne muscular dystrophy.
U.S. Food and Drug Administration. (2023). Exondys 51 (eteplirsen) prescribing information.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations.
U.S. Food and Drug Administration. (2024). Guidance for industry: 180-day exclusivity when multiple first applicants are submitted.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Sarepta Theraps Inc	EXONDYS 51	eteplirsen	SOLUTION;INTRAVENOUS	206488-001	Sep 19, 2016		RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial				TREATMENT OF DUCHENNE MUSCULAR DYSTROPHY IN PATIENTS HAVING A MUTATION OF THE DMD GENE THAT IS AMENABLE TO EXON 51 SKIPPING	⤷ Start Trial
Sarepta Theraps Inc	EXONDYS 51	eteplirsen	SOLUTION;INTRAVENOUS	206488-002	Sep 19, 2016		RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial				TREATMENT OF DUCHENNE MUSCULAR DYSTROPHY IN PATIENTS HAVING A MUTATION OF THE DMD GENE THAT IS AMENABLE TO EXON 51 SKIPPING	⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2014233456	⤷ Start Trial
Australia	2019203505	⤷ Start Trial
Australia	2020260492	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 10,337,003

Which drugs does patent 10,337,003 protect, and when does it expire?

Summary for Patent: 10,337,003