United States Drug Patent RE47769: Claim Scope, Eteplirsen Coverage, Expiration Risk, and Patent Landscape

U.S. Patent RE47769 covers sequence-defined antisense oligonucleotides directed to dystrophin exon 51, including morpholino antisense oligomers and certain injectable formulations. The claim set is most closely associated with eteplirsen, marketed by Sarepta Therapeutics as Exondys 51. The broadest protection is in claim 1, while claims 22 through 33 narrow protection to a 30-nucleotide sequence, morpholino chemistry, polyethylene glycol linkage, injectable formulation, and specified administration routes.[1,2]

The patent is a reissue patent. A reissue does not reset the underlying patent term. Its enforceable term is tied to the original patent's expiration date, subject to applicable patent-term adjustment, terminal disclaimers, and any other statutory limitations.[3]

What drug does U.S. Patent RE47769 protect?

RE47769 protects an antisense oligonucleotide that binds a target sequence in dystrophin pre-mRNA and is intended to alter splicing by inducing exon 51 skipping.

The covered 30-nucleotide sequence is:

5′-CUCCAACAUCAAGGAAGAUGGCAUUUCUAG-3′

With uracil-to-thymine substitution, the corresponding DNA-style sequence is:

5′-CTCCAACATCAAGGAAGATGGCATTTCTAG-3′

This sequence is associated with eteplirsen, an exon 51-skipping phosphorodiamidate morpholino oligomer, or PMO. Exondys 51 received accelerated FDA approval in September 2016 for Duchenne muscular dystrophy patients with a confirmed mutation amenable to exon 51 skipping.[2]

RE47769 does not claim every exon 51-skipping drug. Its claims depend on the specific sequence, sequence length, backbone chemistry, conjugation, formulation, or administration limitations stated in each claim.

What is the broadest claim in RE47769?

Claim 1 is the broadest independent composition claim:

An isolated antisense oligonucleotide of 30 to 50 nucleotides comprising SEQ ID NO: 181, with uracil optionally replaced by thymine.

The principal scope elements are:

Element	Claim requirement
Molecule type	Isolated antisense oligonucleotide
Length	30 to 50 nucleotides
Sequence	Must comprise SEQ ID NO: 181
Base variation	Uracil may be replaced with thymine
Targeting concept	Sequence-defined antisense activity
Backbone	Not limited in claim 1
RNase H	Not excluded until dependent claim 4

The word "comprising" is important. It permits additional nucleotides beyond the recited 30-nucleotide sequence, provided the resulting molecule remains within the 30-to-50-nucleotide range. A 30-nucleotide molecule containing the exact sequence is covered. A longer molecule containing the sequence plus flanking nucleotides may also fall within claim 1.

Claim 1 is broader than eteplirsen as commercially supplied because it does not require PMO chemistry, PEG conjugation, intravenous administration, or a specific carrier.

How do the dependent claims narrow RE47769?

Claims 2 through 21 define chemical variants of the sequence-defined oligomer.

Backbone and sugar modifications

Claims 2 and 5 cover non-natural backbones and non-natural sugar moieties. Claim 6 identifies morpholinos, and claim 7 specifies thymine substitution for uracil.

Claims 8 through 11 focus on modified internucleotide linkages, including:

Methyl phosphonates
Methyl phosphorothioates
Phosphoromorpholidates
Phosphoropiperazidates
Phosphoroamidates

Claim 11 narrows that group to phosphoroamidates.

Claims 12 through 19 combine non-natural sugar moieties with modified internucleotide linkages. Claims 13 through 16 specifically identify morpholinos with modified phosphates and, in the narrower claims, phosphoroamidate linkages and thymine bases.

Claim 18 separately covers phosphoromorpholidate linkages in the claim 10 pathway. Claim 19 does the same in the combined morpholino pathway.

RNase H limitation

Claim 4 requires that the antisense oligonucleotide does not activate RNase H. This limitation is consistent with steric-blocking antisense chemistry, including PMOs. The claim excludes antisense designs that operate through RNase H-mediated degradation if that activity is legally established as part of the accused molecule's operation.

Length limitation

Claims 20 and 21 require a 30-nucleotide oligomer. These claims are particularly relevant to the exact eteplirsen sequence because the recited sequence itself is 30 nucleotides long.

What formulations are protected by RE47769?

Claims 22 through 33 are formulation claims. Each requires the same core product:

A 30-nucleotide antisense oligonucleotide;
The SEQ ID NO: 181 sequence;
Thymine substitution for uracil;
Morpholino chemistry;
Chemical linkage to a polyethylene glycol chain; and
An injectable solution.

The formulation claims then vary the route and vehicle.

Claims	Route	Vehicle limitation
22-24	Intravenous	Pharmaceutically acceptable carrier or diluent; claims 23-24 specify isotonic saline or PBS
25-27	Parenteral	Pharmaceutically acceptable carrier or diluent; claims 26-27 specify isotonic saline or PBS
28-30	Intramuscular	Pharmaceutically acceptable carrier or diluent; claims 29-30 specify isotonic saline or PBS
31-33	Subcutaneous	Pharmaceutically acceptable carrier or diluent; claim 32 specifies isotonic saline

These claims are materially narrower than claim 1. An accused product would need to meet the exact sequence, morpholino structure, PEG linkage, injectable format, and route limitation where applicable.

The claims also contain substantial overlap. Intravenous administration is a form of parenteral administration, so an intravenous formulation could potentially implicate both the intravenous claims and the broader parenteral claims if all other limitations are satisfied.

How strong is the patent estate for eteplirsen?

RE47769 has strong literal scope against products that reproduce the exact sequence and claimed chemistry. Its practical strength is lower against products that use:

A different exon 51-binding sequence;
A different backbone;
A non-PEG conjugate;
A non-injectable formulation;
A different route;
A sequence that binds the same pre-mRNA region but does not comprise SEQ ID NO: 181.

The patent's central commercial value is sequence specificity. A competitor cannot avoid claim 1 merely by replacing uracil with thymine, because the claims expressly permit that substitution. A competitor may, however, challenge whether its sequence contains the claimed 30-nucleotide sequence or whether its chemistry falls within the listed structural limitations.

The formulation claims provide narrower protection and are more vulnerable to design-around strategies. For example, a product using the same biological target but a different oligonucleotide sequence, a non-morpholino backbone, or a non-PEG-linked construct would not satisfy all limitations of claims 22 through 33.

When does RE47769 lose exclusivity?

The reissue date does not establish a new patent term. Under U.S. law, a reissue generally carries the remaining term of the original patent.[3] The relevant expiration analysis therefore requires review of:

The original patent number;
The earliest effective nonprovisional filing date;
Patent-term adjustment;
Any terminal disclaimer;
Any patent-term extension;
Continuation or divisional relationships; and
The USPTO maintenance and legal-status record.

FDA regulatory exclusivity is separate from patent exclusivity. Exondys 51 received accelerated approval, but the approval itself does not extend the term of RE47769. FDA exclusivity and patent rights must be analyzed independently.[2,4]

A generic applicant could challenge an Orange Book-listed patent before expiration through an Abbreviated New Drug Application, or ANDA, containing a Paragraph IV certification. A 30-month stay may apply if the patent holder files timely patent litigation after receiving notice.[5]

What is the Orange Book status of RE47769?

The Orange Book identifies patents submitted by an applicant and accepted for listing in connection with an approved drug product. Patent issuance alone does not establish Orange Book listing.[4]

For Exondys 51, the relevant Orange Book analysis should distinguish:

Composition or sequence patents;
Method-of-use patents;
Formulation patents;
Manufacturing patents;
Patents listed for the approved product versus patents associated with the broader research program.

RE47769 should not be treated as an automatically enforceable Orange Book barrier merely because its claims cover the eteplirsen sequence. The legal significance of the patent depends on whether it was listed for Exondys 51, whether the listing remained active, and whether an ANDA applicant certified to it.

Are there Paragraph IV challenges to eteplirsen?

A Paragraph IV challenge is product-specific and patent-specific. It requires an ANDA applicant to assert that a listed patent is invalid, unenforceable, or would not be infringed by the proposed generic product.[5]

For a sequence-defined PMO, a generic applicant faces several possible paths:

Challenge strategy	Principal issue
Noninfringement	Product does not contain SEQ ID NO: 181 or required chemical features
Invalidity for anticipation	Earlier reference discloses the exact sequence and claimed structure
Obviousness	Whether the claimed sequence and chemistry would have been obvious
Written description	Whether the patent adequately supports the full 30-to-50-nucleotide scope
Enablement	Whether the full claimed genus is enabled
Indefiniteness	Whether terms such as "enhance activity" provide adequate boundaries
Regulatory distinction	Proposed product does not fit the same drug-product category

The broadest claim is more exposed to genus-scope arguments than the narrow formulation claims. Claim 1 covers a sequence-containing range and broad backbone choices. Claims 22 through 33 contain more structural limitations, which can make them easier to distinguish but harder to invalidate on broadness grounds.

What generic-entry risks exist for Exondys 51?

The principal generic-entry risks are sequence identity, chemistry, and regulatory substitutability.

A conventional small-molecule ANDA model does not map cleanly onto a PMO antisense product. The FDA may require detailed characterization of oligonucleotide identity, impurity profile, molecular distribution, stereochemistry where relevant, conjugation, formulation, and biological activity. The applicant must also establish pharmaceutical equivalence and bioequivalence under the applicable regulatory framework.[5,6]

Potential launch scenarios include:

Direct sequence-copying product. Highest infringement risk under claim 1 and the morpholino claims.
Same sequence with different backbone. Potential exposure under claim 1, but potentially outside claims limited to morpholinos or modified phosphates.
Alternative exon 51 sequence. Lower risk under RE47769 if the alternative does not comprise SEQ ID NO: 181.
Same sequence without PEG. Lower risk under claims 22 through 33, but not necessarily under claim 1 or claims 2 through 21.
Different route or non-injectable presentation. May avoid the formulation claims while leaving composition claims relevant.

How does RE47769 compare with competing DMD antisense patents?

Product	Company	Target	Chemistry	Relationship to RE47769
Exondys 51, eteplirsen	Sarepta	DMD exon 51	PMO	Closest product and sequence match
Vyondys 53, golodirsen	Sarepta	DMD exon 53	PMO	Different sequence and target
Viltepso, viltolarsen	NS Pharma/Nippon Shinyaku	DMD exon 53	PMO	Different exon 53 sequence
Amondys 45, casimersen	Sarepta	DMD exon 45	PMO	Different sequence and target
Drisapersen	BioMarin, formerly Prosensa	DMD exon 51	2′-O-methyl phosphorothioate	Different chemistry and sequence architecture

The exon target alone does not determine infringement. Eteplirsen, drisapersen, and other exon 51 programs may address the same therapeutic objective while using different sequences and backbones. RE47769 is therefore not a platform patent covering all exon 51 skipping.

What licensing and litigation issues affect the patent?

The relevant commercial rights involve Sarepta's Exondys 51 program and the underlying antisense technology. Sarepta acquired substantial Duchenne muscular dystrophy assets and intellectual property from AVI BioPharma, now known as Entrada Therapeutics' predecessor structure in certain historical records, and through related transactions involving exon-skipping programs. The ownership chain for RE47769 must be distinguished from licenses covering other PMO technologies or different DMD sequences.

Patent litigation risk includes:

Ownership and assignment disputes;
Written-description and enablement challenges;
Sequence noninfringement disputes;
Claim construction involving "comprising SEQ ID NO: 181";
Whether PEG linkage is present and chemically part of the claimed molecule;
Whether a formulation meets the injectable-solution limitations;
Regulatory approval before patent expiration.

No litigation outcome should be attributed to RE47769 without matching the case docket to the specific patent number. Litigation involving other Sarepta patents, other exon-skipping sequences, or other DMD products does not automatically establish the enforceability or scope of RE47769.

What manufacturing and geographic barriers exist?

PMO manufacturing presents barriers beyond the sequence claim. Commercial production requires controlled synthesis, purification, impurity removal, analytical characterization, and reproducible handling of highly charged oligonucleotide material. PEG conjugation adds another manufacturing and characterization layer.

Geographic protection depends on corresponding foreign family members. U.S. RE47769 does not itself create rights in Europe, Japan, China, or other markets. A global freedom-to-operate review must map:

National counterparts;
Patent-family priority;
Local prosecution outcomes;
Local term adjustments;
Supplementary protection certificates where available;
Claim scope by jurisdiction;
Local product approvals and market-entry rules.

Key Takeaways

RE47769 is a sequence-defined antisense patent closely associated with eteplirsen and DMD exon 51 skipping.
Claim 1 covers a 30-to-50-nucleotide antisense oligomer comprising SEQ ID NO: 181, with uracil-to-thymine substitution permitted.
Claims 2 through 21 add non-natural backbones, morpholinos, modified phosphates, RNase H nonactivation, and related chemistry.
Claims 22 through 33 cover narrower PEG-linked morpholino injectable formulations using saline or PBS and specified administration routes.
The reissue does not restart the patent term. The expiration date follows the original patent term, subject to statutory adjustments.
RE47769 is not a platform patent for all exon 51-skipping drugs or all PMO products.
Generic risk is highest for products copying the exact sequence and morpholino chemistry.
Alternative sequences, non-morpholino backbones, non-PEG products, and different formulations create potential design-around positions.
Orange Book listing, Paragraph IV exposure, and current litigation status require patent-specific review of the FDA and court records.

Frequently Asked Questions

Does RE47769 cover all eteplirsen products?

It covers products that satisfy the relevant claim limitations, particularly the SEQ ID NO: 181 sequence and, for narrower claims, morpholino chemistry, PEG linkage, injectable formulation, and route.

Can a competitor avoid RE47769 by replacing uracil with thymine?

No. The claims expressly state that uracil bases may be replaced with thymine bases.

Does RE47769 cover golodirsen or casimersen?

Not based on the supplied claims. Golodirsen targets exon 53 and casimersen targets exon 45. They use different sequence targets and are subject to separate patent estates.

Are formulation claims 22 through 33 broader than claim 1?

No. They are narrower because they require the exact 30-nucleotide sequence, morpholino chemistry, PEG linkage, injectable formulation, and specified administration conditions.

Does FDA approval extend RE47769?

No. FDA approval and patent term are separate legal regimes. Regulatory exclusivity does not automatically extend the patent term.

References

United States Patent and Trademark Office. (2019). U.S. Patent No. RE47,769: Antisense oligonucleotides and compositions.
U.S. Food and Drug Administration. (2016). FDA grants accelerated approval to first drug for Duchenne muscular dystrophy.
United States Code, 35 U.S.C. §§ 251, 253, 154.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
U.S. Food and Drug Administration. (2024). ANDA submissions: Refuse-to-receive standards and patent certifications.
U.S. Food and Drug Administration. (2021). Development of therapeutic oligonucleotides: Guidance for industry.

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	Y				⤷ Start Trial
Sarepta Theraps Inc	EXONDYS 51	eteplirsen	SOLUTION;INTRAVENOUS	206488-002	Sep 19, 2016		RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial	Y				⤷ 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

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

PCT Information
PCT Filed	June 28, 2005	PCT Application Number:	PCT/AU2005/000943
PCT Publication Date:	January 05, 2006	PCT Publication Number:	WO2006/000057

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
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: RE47769

Which drugs does patent RE47769 protect, and when does it expire?

Summary for Patent: RE47769