Details for Patent: 10,364,431

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Which drugs does patent 10,364,431 protect, and when does it expire?

Patent 10,364,431 protects EXONDYS 51 and is included in one NDA.

This patent has twenty-five patent family members in fourteen countries.

Summary for Patent: 10,364,431

Title:	Compositions for treating muscular dystrophy
Abstract:	Improved compositions and methods for treating muscular dystrophy by administering antisense molecules capable of binding to a selected target site in the human dystrophin gene to induce exon skipping are described.
Inventor(s):	Edward M. Kaye
Assignee:	Biopharma Credit PLC
Application Number:	US15/604,335
Patent Claim Types: see list of patent claims	Use; Composition; Formulation;

US Patent 10,364,431: Eteplirsen Patent Scope, Claims, Exclusivity and Generic-Entry Risk

US Patent 10,364,431 protects a narrow, long-duration treatment regimen for eteplirsen, marketed as Exondys 51, in Duchenne muscular dystrophy patients whose DMD mutations are amenable to exon 51 skipping. The patent does not broadly claim eteplirsen, exon 51 skipping, or all DMD treatment. Its independent claims require intravenous administration of approximately 30 mg/kg once weekly for more than 120 weeks, together with specified patient, corticosteroid, formulation, or therapeutic-outcome limitations.[1]

The commercial importance of the patent depends on whether it is listed in the FDA Orange Book for Exondys 51, its applicable patent-term adjustment or disclaimer, and whether a competing applicant seeks approval for the same long-term regimen. The patent is a method-of-use patent, not a composition-of-matter patent.

What does US Patent 10,364,431 protect?

The patent protects two closely related treatment concepts:

1. Treating DMD by administering eteplirsen under a defined long-term dosing regimen.
2. Restoring the dystrophin mRNA reading frame and inducing dystrophin production through that regimen.

The core limitations are:

Claim element	Required limitation
Disease	Duchenne muscular dystrophy
Genetic status	DMD mutation amenable to exon 51 skipping
Active agent	Eteplirsen or a pharmaceutically acceptable salt
Route	Intravenous administration
Dose	About 30 mg/kg
Frequency	Once weekly
Duration	More than 120 weeks
Claimed result	Delayed disease progression, or restoration of the mRNA reading frame and induced dystrophin production
Formulation	Pharmaceutical composition with a carrier; dependent claims specify buffered solution or phosphate-buffered saline
Patient subgroup	Pediatric patients, including patients age 7 or older
Concomitant treatment	Oral corticosteroid use before, during, or after eteplirsen treatment

The independent claims are claims 1 and 11. Claims 2 through 10 depend from claim 1. Claims 12 through 22 depend from claim 11 or its dependent claims.

How broad are the independent claims?

Claim 1 is a treatment-method claim requiring all of the following:

• a patient with DMD;
• a mutation amenable to exon 51 skipping;
• intravenous administration;
• eteplirsen or an acceptable salt;
• approximately 30 mg/kg;
• once-weekly dosing;
• treatment for more than 120 weeks; and
• delayed disease progression.

Claim 11 has substantially the same dosing and patient limitations but recites restoration of the mRNA reading frame and induction of dystrophin production. It also states that disease progression is delayed.

These claims are materially narrower than a claim covering any use of eteplirsen in DMD. A potentially infringing regimen would generally need to practice each required limitation. A competitor administering a different dose, a different interval, a different route, or a course lasting 120 weeks or less would have a noninfringement position based on the literal claim language, although the doctrine of equivalents could remain relevant depending on the facts.

What does “about 30 mg/kg” mean?

The term “about” creates a dosing range rather than an absolute 30 mg/kg requirement. The patent does not establish a universal numerical boundary for “about.” The scope would depend on intrinsic evidence, including the specification, examples, prosecution history, and any statements made to the USPTO.

A regimen of 30 mg/kg per week is the clearest target. Doses materially above or below 30 mg/kg create a claim-construction issue. The risk increases where the competing regimen is clinically and technically equivalent to the claimed dose and the prosecution history does not limit “about.”

What does “more than 120 weeks” require?

The duration limitation is unusually important. It requires administration beyond 120 weeks, not merely a treatment plan that could continue beyond that point. A patient receiving weekly eteplirsen for 121 weeks or longer is within the literal temporal scope if the other limitations are satisfied.

The limitation creates several practical issues:

• A short clinical trial may not establish infringement of the complete regimen.
• A label authorizing chronic weekly use may create a method-of-use exposure even if individual patients discontinue earlier.
• Prescriber conduct and patient treatment records may become relevant to induced-infringement analysis.
• A competitor may attempt to design around the claim through a different dose, interval, route, or duration.

Which dependent claims add commercial or litigation significance?

Pediatric patients and patients age 7 or older

Claims 2, 3, 5, 8, 12, 13, 15, 18 and 19 narrow the patient population to pediatric patients, with certain claims requiring an age of at least 7 years.

These limitations align with the clinical development population and the FDA-approved use of Exondys 51. They may be commercially significant because DMD is primarily a pediatric-onset disease and Exondys 51 is used predominantly in boys and young men.

Corticosteroid pretreatment

Claims 4 and 14 require oral corticosteroid treatment for at least 24 weeks before the first eteplirsen dose. This limitation can be important in infringement analysis because corticosteroid pretreatment is common in DMD care, but it may not be documented uniformly in every patient record.

Claims 6 through 9 and 16 through 20 cover concurrent corticosteroid use more broadly. The listed corticosteroids include:

• betamethasone;
• budesonide;
• cortisone;
• dexamethasone;
• hydrocortisone;
• methylprednisolone;
• prednisolone; and
• prednisone.

Claim 9 and its counterpart claim 20 cover corticosteroid administration before, during, or after eteplirsen administration. These claims are broader in timing than the 24-week pretreatment claims.

Buffered formulations

Claims 10 and 22 specify phosphate-buffered saline. Claims 21 and 22 also address a pH-buffered solution.

These claims are formulation-dependent but remain method claims. They do not independently create a broad composition patent covering every eteplirsen formulation. Their value is greatest where a competing product uses substantially the same carrier or buffer system and the administration method otherwise falls within the independent claim.

Is US Patent 10,364,431 a composition patent or a method-of-use patent?

US 10,364,431 is a method-of-use patent. Its claims require administering eteplirsen to a defined DMD patient population under a specified regimen.

It does not, based on the quoted claims, claim:

• the eteplirsen molecule itself;
• every antisense oligonucleotide that skips exon 51;
• every pharmaceutical composition containing eteplirsen;
• every intravenous eteplirsen treatment;
• every dose of eteplirsen; or
• every treatment of DMD.

The patent should therefore be analyzed separately from composition, sequence, manufacturing, formulation, and broader exon-skipping patents in the eteplirsen estate.

What is the FDA regulatory status of eteplirsen?

The FDA approved Exondys 51 under the accelerated approval pathway on September 19, 2016, for DMD patients with a confirmed mutation amenable to exon 51 skipping.[2] The approval was based on dystrophin production as a surrogate endpoint that was considered reasonably likely to predict clinical benefit.

The approved product is eteplirsen, an antisense oligonucleotide administered by intravenous infusion. The FDA-approved labeling identifies weekly dosing and the genetically defined exon 51-amenable population.[3]

The approval does not itself establish infringement of every claim in US 10,364,431. Patent infringement depends on the scope of the patent claims, the approved labeling, actual prescribing and administration, and the applicable patent-law standards.

What is the Orange Book status of US Patent 10,364,431?

The Orange Book is the key public record for determining whether a patent is listed against an approved small-molecule or other eligible drug product, together with the associated use code and expiration information.[4]

For Exondys 51, the relevant regulatory product is NDA 206488. A complete current assessment must distinguish among:

• patents listed for eteplirsen;
• patents listed for the approved method of use;
• use codes submitted by the NDA holder;
• patent expiration dates recorded by FDA; and
• any delisting, correction, or patent-term changes.

The quoted claims are facially suitable for method-of-use listing because they cover treatment of the approved genetically defined DMD population. The patent’s practical Orange Book impact depends on the FDA listing record and use code, not on the existence of the patent alone.

When does US Patent 10,364,431 lose exclusivity?

The patent’s expiration date cannot be reliably calculated from the claims alone. The controlling date depends on the earliest effective nonprovisional filing date, patent-term adjustment, any patent-term extension, terminal disclaimer, and the USPTO’s official term calculation under 35 U.S.C. §§ 154 and 156.[5]

The relevant distinction is:

Exclusivity type	Relevance to Exondys 51
Patent term	Determined under the patent statute and USPTO records
FDA orphan-drug exclusivity	May restrict approval of the same drug for the same disease during the statutory period
Pediatric exclusivity	Can add six months to qualifying listed exclusivities
Accelerated-approval status	Concerns evidentiary and postapproval obligations, not patent term
Data exclusivity	Depends on the applicable NDA and statutory pathway
Method-of-use patent	May block or complicate approval for the claimed regimen if listed and properly certified

The patent should not be treated as providing a fixed commercial exclusivity date without confirming the official USPTO and Orange Book records.

What Paragraph IV challenges could target Exondys 51?

A generic or 505(b)(2) applicant seeking approval for a product or use covered by a listed patent could submit a Paragraph IV certification asserting that the patent is invalid, unenforceable, or not infringed under section 505(j)(2)(A)(vii)(IV) of the Federal Food, Drug, and Cosmetic Act.[6]

Likely challenge points include:

Written description and enablement

A challenger could argue that the specification does not adequately support all patients with exon 51-amenable mutations, all pediatric patients, the full “about 30 mg/kg” range, or treatment extending beyond 120 weeks.

Obviousness

The challenger could rely on prior DMD treatment with antisense oligonucleotides, earlier eteplirsen dosing studies, exon-skipping publications, corticosteroid therapy, and clinical evidence available before the relevant priority date.

The central question would be whether a skilled artisan would have had a reasonable expectation that weekly 30 mg/kg treatment continued for more than 120 weeks would delay disease progression.

Indefiniteness

Potential disputes could concern:

• “about 30 mg/kg”;
• “amenable to exon 51 skipping”;
• “disease progression is delayed”;
• “restoring an mRNA reading frame”; and
• “induce dystrophin production.”

The FDA label, specification, examples, and prosecution history would affect the analysis.

Infringement

A challenger could use a different dose, interval, duration, formulation, or treatment population. It could also seek a label that omits the patented method, although the success of a section viii carve-out would depend on the precise Orange Book use code and the remaining approved indications.

Does eteplirsen face biosimilar competition?

Eteplirsen is an antisense oligonucleotide drug, not a protein biologic. A conventional biosimilar application under the Public Health Service Act section 351(k) is therefore not the ordinary pathway for a competing eteplirsen product.

The more relevant pathways are:

• an ANDA under section 505(j), if the product can satisfy pharmaceutical-equivalence and bioequivalence requirements;
• a 505(b)(2) application, where the applicant relies partly on FDA findings for Exondys 51 but submits additional data; or
• a full NDA for a substantially different product or clinical use.

The regulatory and patent risks are not limited to US 10,364,431. A competitor would need to evaluate sequence, purity, impurities, stereochemistry, formulation, manufacturing controls, analytical comparability, delivery, and clinical pharmacology.

How strong is the patent estate for eteplirsen?

The estate should be divided into separate technology categories:

Estate category	Primary risk
Eteplirsen composition or sequence	Direct product and use exposure
Exon 51 skipping	Broad method-of-treatment coverage
DMD treatment regimen	Dose, frequency, duration, and patient limitations
Formulation	Buffer, concentration, stability, and administration
Manufacturing	Oligonucleotide synthesis, purification, and quality controls
Clinical use	Pediatric, corticosteroid, and mutation-defined populations
Regulatory listings	ANDA or 505(b)(2) approval timing

US 10,364,431 is strongest against a competitor that adopts the same weekly 30 mg/kg regimen for the exon 51-amenable population over a chronic treatment period. It is weaker against a product with a clearly different dose or dosing interval, a nonintravenous delivery system, or a label that omits the claimed method.

The patent does not eliminate risk from other patents. A design-around of the 30 mg/kg and 120-week limitations could still encounter broader sequence, composition, formulation, or manufacturing claims.

What litigation and settlement issues affect generic entry?

A Paragraph IV notice concerning a listed Exondys 51 patent could trigger patent litigation under the Hatch-Waxman framework. If suit is filed within the statutory period, FDA approval may be stayed for up to 30 months, subject to statutory exceptions and litigation developments.[6]

The principal litigation questions would be:

1. Is US 10,364,431 listed against the relevant Exondys 51 use?
2. Does the proposed label encourage the claimed long-term regimen?
3. Does the competing product use approximately 30 mg/kg weekly?
4. Does the product target exon 51-amenable mutations?
5. Is the 120-week duration limitation satisfied or induced?
6. Are the claims valid over the clinical and scientific prior art?
7. Does any settlement restrict launch timing or impose a license?

No settlement terms should be inferred without an executed agreement, court filing, or authorized regulatory disclosure. A settlement could permit an agreed launch date before patent expiration, but it would not necessarily invalidate or narrow the patent.

What geographic coverage does the patent provide?

US 10,364,431 provides territorial rights in the United States and its applicable territories. It does not directly block treatment, manufacture, sale, or importation in Europe, Japan, China, or other jurisdictions.

International risk must be assessed family by family. The relevant questions are whether corresponding applications were filed, which claims were granted, whether prosecution narrowed them, and whether local patent terms remain in force. The US claims should not be assumed to predict the scope or validity of foreign counterparts.

What generic launch scenarios exist?

Launch scenario	Risk under US 10,364,431
Same eteplirsen product, 30 mg/kg weekly, chronic use	High method-of-use risk
Same product with a label covering exon 51 DMD but no duration language	Significant risk if use code and inducement support coverage
Different weekly dose	Potential design-around; “about” construction is critical
Less frequent administration	Lower literal infringement risk
Nonintravenous delivery	Likely outside the quoted claims
Pediatric-only product	Still within multiple dependent claims
Product used with corticosteroids	Increases exposure to dependent claims
505(b)(2) product with modified formulation	Formulation and method claims require separate analysis
ANDA with a section viii carve-out	Feasible only if the carved-out label avoids the listed patented use

Key Takeaways

• US 10,364,431 is a narrow method-of-use patent for long-term eteplirsen treatment in exon 51-amenable DMD.
• The core regimen is intravenous eteplirsen at about 30 mg/kg once weekly for more than 120 weeks.
• The patent has separate claim groups for disease treatment, mRNA reading-frame restoration, pediatric patients, corticosteroid use, and buffered formulations.
• It does not broadly claim eteplirsen, all exon 51 skipping, or every DMD treatment.
• The “about 30 mg/kg” and “more than 120 weeks” limitations are central to both infringement and validity.
• Eteplirsen is not ordinarily challenged through the biosimilar pathway. ANDA and 505(b)(2) strategies are more relevant.
• Orange Book listing, use-code language, official patent term, and any terminal disclaimer determine the patent’s practical impact on generic entry.
• A competitor may have design-around options involving dose, interval, duration, route, or formulation, but other patents in the eteplirsen estate may remain relevant.

FAQs About US Patent 10,364,431 and Exondys 51

Does US Patent 10,364,431 cover all patients who receive Exondys 51?

No. The quoted claims require an exon 51-amenable DMD mutation, intravenous administration, approximately 30 mg/kg weekly dosing, and treatment for more than 120 weeks, among other limitations.

Can a generic avoid the patent by using a dose other than 30 mg/kg?

Potentially. A materially different dose may avoid literal infringement, but the scope of “about 30 mg/kg” and the doctrine of equivalents must be assessed against the patent record.

Does the patent cover eteplirsen manufacturing?

No. The quoted claims are treatment-method claims. Manufacturing protection would require separate process, intermediate, composition, or quality-control claims.

Is a 505(b)(2) application automatically blocked by this patent?

No. The applicant’s exposure depends on the proposed labeling, Orange Book certifications, formulation, dosing regimen, and any other listed Exondys 51 patents.

Does accelerated approval extend the term of US Patent 10,364,431?

No. Accelerated approval is an FDA regulatory pathway. Patent term is governed separately under the Patent Act, including patent-term adjustment and any applicable patent-term extension.

References

1. United States Patent No. 10,364,431, “Methods for treating Duchenne muscular dystrophy,” issued July 30, 2019. United States Patent and Trademark Office.
2. U.S. Food and Drug Administration. (2016, September 19). FDA grants accelerated approval to first drug for Duchenne muscular dystrophy.
3. U.S. Food and Drug Administration. (n.d.). Exondys 51 (eteplirsen) prescribing information, NDA 206488.
4. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book.
5. United States Code, 35 U.S.C. §§ 154, 156.
6. United States Code, 21 U.S.C. § 355(j).

Drugs Protected by US Patent 10,364,431

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						RESTORING AN MRNA READING FRAME TO INDUCE DYSTROPHIN PROTEIN PRODUCTION IN PATIENTS HAVING A MUTATION OF THE DMD GENE THAT IS AMENABLE TO EXON 51 SKIPPING
Sarepta Theraps Inc	EXONDYS 51	eteplirsen	SOLUTION;INTRAVENOUS	206488-001	Sep 19, 2016		RX	Yes	Yes						TREATMENT OF DUCHENNE MUSCULAR DYSTROPHY IN PATIENTS HAVING A MUTATION OF THE DMD GENE THAT IS AMENABLE TO EXON 51 SKIPPING
Sarepta Theraps Inc	EXONDYS 51	eteplirsen	SOLUTION;INTRAVENOUS	206488-002	Sep 19, 2016		RX	Yes	Yes						RESTORING AN MRNA READING FRAME TO INDUCE DYSTROPHIN PROTEIN PRODUCTION IN PATIENTS HAVING A MUTATION OF THE DMD GENE THAT IS AMENABLE TO EXON 51 SKIPPING
Sarepta Theraps Inc	EXONDYS 51	eteplirsen	SOLUTION;INTRAVENOUS	206488-002	Sep 19, 2016		RX	Yes	Yes						TREATMENT OF DUCHENNE MUSCULAR DYSTROPHY IN PATIENTS HAVING A MUTATION OF THE DMD GENE THAT IS AMENABLE TO EXON 51 SKIPPING

International Family Members for US Patent 10,364,431

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2014233456
Australia	2019203505
Australia	2020260492
Brazil	112015022998
Canada	2906812