United States Patent 10,227,590: Scope, Claims, Expiration, and Viltolarsen Patent Landscape

U.S. Patent No. 10,227,590 protects morpholino antisense oligonucleotides that are 20 to 31 bases long, are fully complementary to a consecutive region of exon 53 of human dystrophin pre-mRNA, contain at least 12 consecutive bases corresponding to the disclosed exon 53 sequence, and induce exon 53 skipping. The patent is closely associated with viltolarsen, marketed in the United States as Viltepso by NS Pharma, a U.S. subsidiary of Nippon Shinyaku.

The patent’s principal commercial value is its coverage of exon 53-skipping PMO molecules, including sequence variants that retain the required 12-base contiguous motif. It does not cover every exon 53-skipping technology. Its limitations to morpholino chemistry, a 20-to-31-base length, exact complementarity, and the specified sequence motif create potential design-around boundaries.

What drug and technology does U.S. Patent 10,227,590 protect?

U.S. Patent 10,227,590 protects antisense oligonucleotides directed to exon 53 of the human dystrophin pre-mRNA. The technology is intended for Duchenne muscular dystrophy, or DMD, patients whose mutations can be functionally corrected by skipping exon 53 during dystrophin pre-mRNA processing.

The patent covers:

Claim element	Requirement
Oligonucleotide length	20 to 31 bases
Target	Consecutive bases of exon 53 of human dystrophin pre-mRNA
Sequence identity	100% complementary to the selected target region
Conserved motif	At least 12 consecutive bases corresponding to SEQ ID NO: 195
Chemistry	Morpholino antisense oligonucleotide
Biological effect	Induces exon 53 skipping
Pharmaceutical form	The oligonucleotide or a pharmaceutically acceptable salt
Composition claim	The oligonucleotide plus a pharmaceutically acceptable carrier

The disclosed reference sequence is:

CUG AAG GUG UUC UUG UAC UUC AUC C

The patent treats uracil positions as thymine positions for the antisense oligonucleotide sequence. The corresponding DNA-style representation is:

CTG AAG GTG TTC TTG TAC TTC ATC C

The claim language is directed to the antisense molecule, not merely to the target RNA sequence. A competing product therefore must be assessed against the claimed antisense sequence, length, chemistry, complementarity, and exon-skipping function.

What are the claims of U.S. Patent 10,227,590?

What does independent claim 1 cover?

Claim 1 covers either:

A morpholino antisense oligonucleotide; or
A pharmaceutically acceptable salt of that oligonucleotide.

The molecule must satisfy all of the following conditions:

It contains 20 to 31 bases.
Its base sequence is 100% complementary to consecutive bases in exon 53 of human dystrophin pre-mRNA.
The base sequence contains at least 12 consecutive bases from the disclosed 27-base sequence.
It is a morpholino antisense oligonucleotide.
It induces exon 53 skipping.

The phrase “comprises at least 12 consecutive bases” is important. It does not limit the claim to one single full-length sequence. A claimed molecule can contain additional bases outside the required 12-base block, provided the complete molecule remains within the 20-to-31-base range and is fully complementary to a consecutive exon 53 target region.

The practical scope is therefore a sequence genus rather than a single compound claim.

What does independent claim 2 cover?

Claim 2 covers a pharmaceutical composition containing:

The claimed morpholino antisense oligonucleotide or its pharmaceutically acceptable salt; and
A pharmaceutically acceptable carrier.

Claim 2 is composition-specific. It may be asserted against a drug product, formulation, vial, injectable preparation, or commercial dosage form containing a qualifying exon 53-skipping morpholino.

Claim 2 does not require a particular carrier, concentration, buffer, pH, dosing schedule, or administration route in the claim text provided. Those details may appear in the specification or dependent claims, but they do not narrow the two independent claims quoted by the user.

How broad is the sequence coverage?

The sequence coverage is materially broader than a single named commercial sequence but narrower than a general exon 53-skipping claim.

Covered sequence architecture

A qualifying molecule must:

Be 20 to 31 bases long;
Include a contiguous 12-base segment from the patent’s reference sequence;
Be fully complementary to a consecutive exon 53 region; and
Use morpholino chemistry.

The 12-base requirement creates multiple possible overlapping sequence variants. A 20-base oligonucleotide can include the required 12-base motif with additional flanking bases. Longer 21-to-31-base molecules can contain even more flanking sequence, subject to the requirement that the whole sequence be complementary to a consecutive exon 53 region.

The claim does not appear to require:

A particular 5' or 3' chemical modification;
A specific morpholino backbone subtype beyond the claim’s morpholino limitation;
A specific salt;
A particular dose;
A particular formulation excipient;
A particular route of administration; or
A particular patient mutation.

What is excluded from the literal scope?

The literal claims do not cover a molecule that lacks any of the following:

Morpholino chemistry;
A 20-to-31-base length;
Exact complementarity to a consecutive exon 53 region;
At least 12 consecutive bases from the stated sequence motif; or
Exon 53-skipping activity.

Potentially outside the literal scope are:

RNA or DNA antisense molecules that are not morpholinos;
Peptide-conjugated molecules if the conjugate changes the claimed chemical identity or falls outside the morpholino limitation;
Molecules shorter than 20 bases or longer than 31 bases;
Molecules containing mismatches to the exon 53 target;
Exon 53-skipping molecules directed to a different target region that does not include the claimed 12-base sequence;
Molecules that target another exon, including exon 51 or exon 45.

Whether a modified or conjugated PMO remains within the claim would depend on its chemical structure and whether the modification is viewed as part of the claimed morpholino antisense oligonucleotide.

What drug is associated with this patent?

The commercial product most closely associated with the patent is viltolarsen, also known as NS-065/NCNP-01. In the United States, viltolarsen is marketed as Viltepso by NS Pharma for treatment of DMD patients with a mutation amenable to exon 53 skipping.

The FDA approved Viltepso on an accelerated-approval basis on August 12, 2020, based primarily on dystrophin production as a surrogate endpoint. The approved product is an intravenous morpholino antisense oligonucleotide directed to exon 53 of dystrophin pre-mRNA. [1]

Viltolarsen is not a biologic. A future competitor would generally pursue an abbreviated new drug application, a 505(b)(2) application, or another applicable small-molecule/oligonucleotide pathway rather than a biosimilar application under the Public Health Service Act.

What is the Orange Book status of U.S. Patent 10,227,590?

U.S. Patent 10,227,590 has been associated with the U.S. regulatory protection for Viltepso and appears in the FDA’s Orange Book patent listings for the product. The relevant listing should be evaluated together with any later-added patents, pediatric exclusivity, and FDA listing updates. [2]

Regulatory item	Status
Product	Viltepso
Active ingredient	Viltolarsen
Sponsor	NS Pharma, Inc.
FDA application	NDA 212154
Approval pathway	Accelerated approval
Patent relevance	Exon 53-skipping morpholino composition and pharmaceutical composition
Patent number	U.S. 10,227,590
Nominal patent expiration	Approximately November 2035, before any applicable patent-term adjustment or extension
Exclusivity type	Patent protection plus regulatory exclusivity associated with the approval

The patent’s enforceability period is not necessarily identical to the commercial exclusivity period. Regulatory exclusivity and patent term operate independently. Patent-term adjustment, patent-term extension, pediatric exclusivity, later-listed patents, or enforcement outcomes can alter the effective generic-entry analysis.

When does U.S. Patent 10,227,590 lose exclusivity?

The patent’s ordinary statutory term is expected to run into November 2035, calculated from the relevant international or nonprovisional filing date. The patent issued on March 12, 2019. [3]

A practical exclusivity timeline is:

Event	Date or period
Priority and international patent filings	2014-2015 family period
U.S. patent publication and national-stage prosecution	2017 period
Patent issuance	March 12, 2019
FDA approval of Viltepso	August 12, 2020
Nominal patent expiry	Approximately November 2035
Earliest ordinary post-expiry generic opportunity	Subject to FDA exclusivity and litigation, generally after patent expiry

A generic applicant may file an ANDA before patent expiry and certify against the listed patent. A Paragraph IV certification can trigger patent litigation and a potential 30-month stay of approval under the Hatch-Waxman Act. [4]

What Paragraph IV challenges could be brought against this patent?

A generic or 505(b)(2) applicant could challenge U.S. 10,227,590 through a Paragraph IV certification on several grounds:

Anticipation

The challenger would need to identify a single prior-art reference disclosing every claim limitation, including:

A 20-to-31-base morpholino;
Exact complementarity to consecutive exon 53 bases;
At least 12 consecutive bases from the claimed motif; and
Exon 53-skipping activity.

A prior-art reference that discloses exon 53 skipping generally may not anticipate the claim if it does not disclose the specific claimed sequence architecture.

Obviousness

An obviousness challenge could combine prior art on:

Dystrophin exon 53 skipping;
PMO chemistry;
The claimed exon 53 sequence;
Antisense length optimization; and
Screening of neighboring target sequences.

The strongest defense for the patent would be evidence that the claimed sequence produced an unexpected exon-skipping or dystrophin-restoration result compared with other exon 53-targeting PMOs.

Written description and enablement

A challenger could argue that the claimed genus covers a large number of possible 20-to-31-base molecules but the specification does not adequately demonstrate or enable the full range. The patent holder would rely on sequence disclosures, experimental data, and the predictable relationship between antisense complementarity and exon recognition.

The most important enablement issue is whether the disclosed data support the full genus of sequences containing the 12-base motif, rather than only a limited number of tested sequences.

Claim construction

Potential disputes include:

The meaning of “at least 12 consecutive bases”;
Whether the 12-base segment must be identical to a contiguous portion of SEQ ID NO: 195 in the claimed orientation;
The meaning of “morpholino antisense oligonucleotide”;
Whether a chemically modified PMO remains within the morpholino limitation;
Whether “induces exon 53 skipping” is a structural limitation, a functional limitation, or both; and
Whether exact complementarity is required across the entire claimed sequence or only across the exon 53 target region.

Which companies are challenging or competing with this patent?

The principal commercial competitor in exon 53 skipping is Sarepta Therapeutics, whose golodirsen product is marketed as Vyondys 53.

Product	Company	Chemistry	Target exon	FDA status
Viltepso, viltolarsen	NS Pharma/Nippon Shinyaku	Morpholino antisense oligonucleotide	Exon 53	Approved
Vyondys 53, golodirsen	Sarepta Therapeutics	Morpholino antisense oligonucleotide	Exon 53	Approved
Exondys 51, eteplirsen	Sarepta Therapeutics	Morpholino antisense oligonucleotide	Exon 51	Approved
Amondys 45, casimersen	Sarepta Therapeutics	Morpholino antisense oligonucleotide	Exon 45	Approved

Golodirsen is commercially relevant because it uses the same broad PMO platform and targets the same exon, but it is not automatically outside U.S. 10,227,590. A freedom-to-operate determination requires a sequence comparison against SEQ ID NO: 195, the molecule’s length, and the specific exon 53 target region.

Competition based on the same exon does not establish patent infringement. Two PMOs can induce skipping of exon 53 while targeting different sequences or using different claimed chemistries.

How does U.S. 10,227,590 compare with the patent estate for golodirsen?

The two products compete clinically and commercially but may rely on different patent families.

Issue	Viltolarsen estate	Golodirsen estate
Commercial sponsor	NS Pharma/Nippon Shinyaku	Sarepta Therapeutics
Target	Dystrophin exon 53	Dystrophin exon 53
Core chemistry	Morpholino	Morpholino
Patent 10,227,590 relevance	Directly directed to exon 53 PMOs containing the claimed sequence motif	Relevant only if the golodirsen sequence satisfies all claim limitations
Key distinction	Claimed motif, length, exact complementarity, exon-skipping function	Product-specific sequence and separate Sarepta patent families
Biosimilar pathway	Not applicable	Not applicable
Generic risk	ANDA or 505(b)(2), subject to Orange Book patents	ANDA or 505(b)(2), subject to Sarepta patents

The central competitive question is not whether both drugs are PMOs or whether both skip exon 53. It is whether the accused product contains the claimed 12-base motif and otherwise satisfies every limitation of claim 1 or claim 2.

What formulations are protected by the patent?

Claim 2 protects a pharmaceutical composition containing a qualifying antisense oligonucleotide and a pharmaceutically acceptable carrier. The claim is broad as written because it does not identify a single buffer, preservative, tonicity agent, concentration, or container.

The composition claim can reach a finished injectable product if:

The product contains the claimed exon 53-skipping morpholino; and
The product contains a pharmaceutically acceptable carrier.

The claim does not necessarily protect:

A formulation containing a non-morpholino exon 53 antisense agent;
A formulation containing a morpholino that lacks the required 12-base motif;
A formulation in which the active agent is not fully complementary to a consecutive exon 53 region; or
A carrier-only formulation.

A separate formulation patent would provide stronger protection for a specific concentration, pH, excipient combination, stability profile, or dosing presentation. The two claims supplied by the user do not contain those narrower formulation limitations.

What manufacturing and intellectual-property barriers affect generic entry?

Manufacturing may be a greater practical barrier than the basic composition claim. PMOs are synthetic oligonucleotides that require control of:

Sequence fidelity;
Backbone chemistry;
Chain-length distribution;
Deletion and insertion impurities;
Residual reagents;
Aggregation;
Sterility;
Endotoxin;
Container compatibility; and
Batch-to-batch analytical comparability.

An ANDA applicant would also need to establish pharmaceutical equivalence and adequate quality controls. The applicant would not normally need to reproduce every manufacturing step used by NS Pharma, but it would need a commercially reliable process that produces the same active ingredient and meets FDA quality requirements.

The patent creates a legal barrier for products using the claimed sequence architecture. Manufacturing know-how, analytical methods, process patents, and formulation patents could create additional barriers even if a challenger avoids literal infringement of U.S. 10,227,590.

What geographic coverage does the patent provide?

U.S. Patent 10,227,590 provides rights only in the United States. It does not directly control manufacture, sale, importation, or use in Europe, Japan, China, or other jurisdictions.

The relevant international patent family should be reviewed separately for:

European Patent Office members;
Japan;
China;
South Korea;
Canada;
Australia; and
Other markets where viltolarsen is approved or commercially planned.

The scope and enforceability of foreign counterparts can differ because of local claim construction, opposition outcomes, supplementary protection certificates, patent-term adjustments, and national prosecution amendments.

How strong is the patent estate for viltolarsen?

U.S. 10,227,590 is commercially meaningful because it combines four limitations that align closely with viltolarsen’s product profile:

Exon 53 targeting;
Morpholino chemistry;
A defined sequence motif; and
Demonstrated exon-skipping activity.

Its strength is reduced by the same limitations. A competitor may attempt to design around the patent by changing:

The target window within exon 53;
The sequence so it lacks the required 12-base motif;
The antisense chemistry;
The molecule length;
The number or location of chemical modifications; or
The exon target.

The doctrine of equivalents could limit some design-around strategies, but it cannot be assumed to eliminate express claim limitations. A molecule with non-morpholino chemistry or a sequence outside the claimed motif would present a materially different infringement analysis.

What generic launch scenarios exist?

Scenario 1: No successful early challenge

The patent remains enforceable through its nominal November 2035 term. Generic or 505(b)(2) approval may be delayed by the patent listing, FDA exclusivity, litigation, or settlement terms.

Scenario 2: Paragraph IV litigation

An ANDA applicant files a Paragraph IV certification. The patent owner sues within the statutory period, triggering a potential 30-month stay. The case could end through invalidity, non-infringement, settlement, or a judgment sustaining the patent.

Scenario 3: Successful sequence design-around

A competitor develops an exon 53-skipping PMO that lacks the claimed 12-base motif or uses non-morpholino chemistry. Regulatory approval would still require clinical and CMC support, but the product could reduce exposure to this patent.

Scenario 4: 505(b)(2) entry

A sponsor relies partly on existing viltolarsen data while introducing a modified formulation, delivery system, or dosing approach. The sponsor would face patent certifications and possible exclusivity restrictions.

Scenario 5: Post-expiry entry

After patent expiry and expiration of applicable regulatory exclusivities, multiple PMO suppliers could compete. The technical complexity of PMO manufacturing and the small genetically defined patient population could limit the number of entrants.

Key Takeaways

U.S. Patent 10,227,590 claims morpholino antisense oligonucleotides targeting exon 53 of dystrophin pre-mRNA.
Claim 1 is a sequence-and-function claim covering 20-to-31-base PMOs with at least 12 consecutive bases from SEQ ID NO: 195.
Claim 2 extends protection to pharmaceutical compositions containing the claimed PMO and a pharmaceutically acceptable carrier.
The patent is closely associated with viltolarsen, marketed as Viltepso by NS Pharma.
The nominal patent term runs into November 2035, subject to any applicable term adjustment or extension.
Golodirsen and viltolarsen compete in exon 53 skipping, but shared target exon and PMO chemistry do not by themselves establish infringement.
The main design-around options are a different exon 53 sequence, non-morpholino chemistry, a different length, or a target lacking the claimed 12-base motif.
Generic entry would normally proceed through an ANDA or 505(b)(2) pathway, not a biosimilar application.
PMO manufacturing controls, sequence analytics, sterile injectable production, and regulatory requirements remain meaningful commercial barriers after patent expiry.

FAQs About U.S. Patent 10,227,590

Does the patent cover all exon 53-skipping antisense drugs?

No. It is limited to morpholino antisense oligonucleotides with the claimed length, sequence, complementarity, and exon-skipping characteristics.

Is golodirsen automatically covered by U.S. Patent 10,227,590?

No. Golodirsen must be compared with every limitation of the asserted claim, including the 12-base sequence motif and exact complementarity requirement.

Is U.S. Patent 10,227,590 a biologic patent?

No. The patent covers a chemically synthesized morpholino antisense oligonucleotide. A competing product would not ordinarily use the biosimilar pathway solely because it competes with viltolarsen.

Can a longer exon 53 PMO avoid the patent?

Possibly, but not merely because it is longer. Molecules up to 31 bases remain within the stated length range if they satisfy the sequence, complementarity, chemistry, and functional limitations.

Does claim 2 protect the Viltepso vial and formulation?

Claim 2 can cover a pharmaceutical composition containing the claimed PMO and a pharmaceutically acceptable carrier. Whether a specific Viltepso presentation infringes requires comparison of its active ingredient and composition with the claim limitations.

References

U.S. Food and Drug Administration. (2020). FDA grants accelerated approval to first drug for Duchenne muscular dystrophy amenable to exon 53 skipping. https://www.fda.gov
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.accessdata.fda.gov/scripts/cder/ob/
United States Patent and Trademark Office. (2019). U.S. Patent No. 10,227,590, Antisense oligonucleotide inducing exon skipping in dystrophin gene. https://patents.google.com
U.S. Food and Drug Administration. (2017). Abbreviated new drug application submissions: Refuse-to-receive standards. https://www.fda.gov wag.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Australia	2004903474	Jun 28, 2004

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	E498685	⤷ Start Trial
Cyprus	1111447	⤷ Start Trial
Cyprus	1117475	⤷ Start Trial
Germany	602005026386	⤷ Start Trial
Denmark	1766010	⤷ Start Trial
Denmark	2206781	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 10,227,590