United States RE47751 (Dystrophin Exon 51 Skipping): Scope of Claims, Coverage Boundaries, and US Patent Landscape
United States RE47751 is directed to methods for inducing exon 51 skipping in a dystrophin gene using an antisense oligonucleotide (30 to 50 nt) comprising SEQ ID NO: 181, including a constraint that uracil bases are optionally replaced with thymine bases. Dependent claim features narrow coverage by (i) requiring SEQ ID NO: 181 as the sole oligo sequence, (ii) limiting or excluding RNase H activation, (iii) requiring non-natural backbones and optionally morpholino chemistry, (iv) requiring non-natural internucleotide linkages with optional “modified phosphate” classes, and (v) specifying further delivery enhancement via conjugates including PEG. The broadest US claim set is method-of-treatment coverage (inducing skipping, correcting/restoring dystrophin) rather than standalone composition claims.
What does RE47751 claim cover for dystrophin exon 51 skipping methods?
Core independent coverage (claim 1):
A method of inducing skipping of exon 51 in a dystrophin gene in a subject by administering a pharmaceutical composition comprising:
- An antisense oligonucleotide (30 to 50 nucleotides)
- Comprising SEQ ID NO: 181
- With uracil bases optionally replaced by thymine bases
- With a pharmaceutically acceptable carrier
Functional scope captured by follow-on independent-style method claims:
- Claim 19: method of correcting a defective dystrophin gene using the same oligo/carrier framework.
- Claim 22: method of restoring or increasing functional dystrophin protein production using the same oligo/carrier framework.
- Claim 25: method of treating muscular dystrophy associated with a defective dystrophin gene using the same oligo/carrier framework.
What specific exon skipping target is required?
- The claims are expressly limited to exon 51 skipping in the dystrophin gene (claim 1).
- The muscular dystrophy treatment claims (claim 25) cover dystrophin defects generically, while subclaims specify Duchenne and Becker contexts.
What is the minimum oligonucleotide length constraint?
- The method claims require an antisense oligonucleotide length of 30 to 50 nucleotides (claims 1, 19, 22, 25).
What is the SEQ ID NO: 181 “uracil vs thymine” design boundary?
- The claims cover antisense oligonucleotides where uracil bases are optionally thymine bases.
- The more specific injectable-solution claims (claims 32–35) lock thymine usage for the listed sequence.
What patient population is covered?
- Claim 4: subject is a human.
- Claim 28: muscular dystrophy is Becker muscular dystrophy.
- Claim 29: muscular dystrophy is Duchenne muscular dystrophy.
- The injectable-solution claims (claims 32–35) specify “human patient.”
What are the key dependent claim features that narrow RE47751 coverage?
RNase H activation limitation (claim 5)
- Coverage can require that the antisense oligonucleotide does not activate RNase H.
This is a meaningful boundary for chemistry choices that can shift mechanism (RNase H cleavage typically aligns with many DNA-like or phosphorothioate designs; RNase H-independent strategies are often used for certain steric oligo approaches).
Non-natural backbone and sugar constraints (claims 6–8, 11–12)
- Claim 6: the oligonucleotide comprises a non-natural backbone.
- Claim 7: sugar moieties are replaced with non-natural moieties.
- Claim 8: the non-natural moieties are morpholinos.
- Claim 11: both sugar moieties are replaced with non-natural moieties and the internucleotide linkages are replaced with non-natural linkages.
Non-natural internucleotide linkage constraints and “modified phosphates” (claims 9, 10, 13)
- Claim 9: internucleotide linkages are replaced with non-natural inter-nucleotide linkages.
- Claim 10: modified phosphates as the subclass.
- Claim 13: examples/limit to modified phosphates including:
- methyl phosphonates
- methyl phosphorothioates
- phosphoromorpholidates
- phosphoropiperazidates
- phosphoroamidates
Specific oligo modalities (claims 14–15)
- Claim 14: oligonucleotide is 2′-O-methyl-oligoribonucleotide.
- Claim 15: oligonucleotide is a peptide nucleic acid (PNA).
Conjugation and delivery enhancement (claims 16–18)
- Claim 16: oligo is chemically linked to one or more moieties/conjugates that enhance activity, cellular distribution, or uptake.
- Claim 17: conjugated to a polyamine.
- Claim 18: conjugated to a polyethylene glycol (PEG) chain.
Phosphate-buffered saline carrier limitation (claim 30)
- Claim 30 requires pharmaceutical carrier as phosphate buffered saline.
Steroid co-administration (claim 31)
- Claim 31 adds a method step: administering a steroid.
What do the injectable solution claims add to RE47751’s practical coverage?
Claims 32–35 convert the method format into an explicitly defined injectable, intravenously administered solution with specific chemical embodiment constraints.
Claims 32–35 share a single defined oligonucleotide sequence and chemistry
Each claim recites an antisense oligonucleotide of 30 nucleotides comprising:
- Base sequence: 5′-CUCCAACAUCAAGGAAGAUGGCAUUUCUAG-3′ (SEQ ID NO: 181)
- uracil bases are thymine bases
- morpholino antisense oligonucleotide
- chemically linked to a polyethylene glycol chain
- The composition is in phosphate-buffered saline
- Formulated for intravenous administration
- And directed to exon skipping, correcting, restoring, or treating Duchenne.
Distinct treatment scope within injectable claims
- Claim 32: inducing exon 51 skipping in a human patient (injectable IV solution).
- Claim 33: correcting defective dystrophin gene in a human patient (injectable IV solution).
- Claim 34: restoring/increasing functional dystrophin protein in a human patient (injectable IV solution).
- Claim 35: treating Duchenne muscular dystrophy in a human patient (injectable IV solution).
Practical implication for design-arounds:
Any generic/competitor program attempting to avoid RE47751 method claim coverage must evaluate:
- whether it uses an oligo that still “comprises SEQ ID NO: 181” under the claim’s framing,
- whether oligo length remains within 30–50 nt,
- whether the chemistry includes the dependent constraints (morpholino backbone, PEG conjugate, modified phosphates),
- and whether administration uses IV PBS formulations that fall under the injectable dependent claims.
How do the claims read together: what is the effective “coverage envelope”?
RE47751’s claim set has two layers:
-
Sequence-and-length-and-carrier layer (breadth):
- 30–50 nt antisense oligo comprising SEQ ID NO: 181
- uracil optionally thymine
- administered in a pharmaceutically acceptable carrier
- applies to methods of exon 51 skipping, correction, restoring dystrophin production, and muscular dystrophy treatment tied to dystrophin defects.
-
Mechanism-and-chemistry layer (narrowing via dependents):
- non-natural backbone and sugar replacements
- morpholino option
- non-natural internucleotide linkages and modified phosphate categories
- RNase H non-activation
- optionally 2′-O-methyl or PNA embodiments
- conjugation options including PEG, polyamine
- carrier PBS and steroid co-administration
- explicit IV injectable solution with morpholino + PEG for the 30-nt thymine-fixed sequence.
Key point for infringement mapping:
Because the claims are framed as dependent methods, coverage depends on which embodiment is practiced. A competitor that practices the “injectable IV morpholino-PEG with PBS” embodiment risks hitting claims 32–35 if all elements match. A different chemistry that still uses an SEQ ID NO: 181 antisense sequence within 30–50 nt may still fall into the independent method claims (claims 1, 19, 22, 25) depending on interpretation of “optionally thymine bases” and “comprising SEQ ID NO: 181.”
What patent estate questions matter most for RE47751 in US?
Is RE47751 about composition or method-of-use?
On its face, the provided claims are method-of-treatment claims. The core “administering a pharmaceutical composition comprising…” language functions as a method-of-use frame, but the claim itself is directed to the act of administering for dystrophin correction/exon skipping.
What claim elements are most likely to be litigated?
For method claims in antisense oligonucleotide programs, typical contested issues map directly to RE47751’s limitations:
- Whether an accused oligonucleotide “comprises SEQ ID NO: 181” (sequence identity, base substitutions, length, and whether the claim treats the sequence as defining the antisense region).
- Whether the chemistry meets “non-natural backbone” and/or morpholino and/or modified phosphate internucleotide linkage limitations (if those dependent claims are asserted).
- Whether the oligo does not activate RNase H (claim 5), which can become an assay-and-mechanism issue.
- Whether the accused product is administered in the specified injectable IV PBS form with morpholino + PEG conjugate (claims 32–35).
When does RE47751 lose exclusivity?
No expiration, priority, or reissue details were provided with the claim text. Without those filing and priority facts, the exclusivity and patent term timeline cannot be calculated accurately.
What Paragraph IV or biosimilar risk exists for RE47751?
RE47751 is not framed as a biologic, and the provided claims are method-of-use for antisense oligonucleotide exon 51 skipping. Paragraph IV risk and ANDA/BLA-style entry mechanics depend on whether the relevant drug is approved under ANDA-capable pathways and whether the Orange Book lists corresponding patents for the approved product. No FDA listing or regulatory linkage data is provided, so a precise Paragraph IV or biosimilar risk assessment cannot be produced from the information given.
What is the Orange Book status of RE47751?
No Orange Book listing identifiers (NDA/BLA number, listed drug, patent list number, or expiration) were provided. Without those, Orange Book status cannot be stated.
Which companies are challenging RE47751 in court?
No litigation docket, parties, venue, or asserted claims were provided. Without that, the challenged landscape cannot be mapped.
What generic entry risks exist for exon 51 skipping antisense oligonucleotides like SEQ ID NO: 181?
Entry risk for antisense method claims depends on:
- whether an entrant uses substantially the same oligo sequence definition as SEQ ID NO: 181,
- whether base substitutions fall within “uracil optionally thymine,”
- and whether the entrant’s formulation and administration match key dependent limitations (morpholino backbone, PEG conjugation, IV PBS formulation).
No product-level composition/formulation and regulatory entry data was provided, so no probability-weighted launch scenario can be stated.
How does RE47751 compare with adjacent dystrophin exon skipping patent claim patterns?
Across exon skipping and antisense exon-targeting portfolios, patent estates often split into:
- sequence-specific antisense molecules,
- backbone chemistry and linkage choices,
- RNase H activation or steric mechanism constraints,
- conjugation/delivery enhancements,
- formulation and route claims (IV/subcutaneous, buffer),
- and exon skipping method-of-use.
RE47751 follows that pattern by combining a sequence constraint (SEQ ID NO: 181) with optional base chemistry (uracil vs thymine), then adding optional dependents that can be used to assert coverage against different product embodiments.
Claim chart style mapping: which elements are “must-match” versus “optional”?
| Claim element |
Present in all independent method claims |
Present only in dependents / specific injectables |
Practical effect |
| Exon 51 skipping |
Yes (claim 1) |
Some dependents align |
Must satisfy target biology for claim 1-type infringement theories |
| SEQ ID NO: 181 |
Yes (claims 1, 19, 22, 25) |
Yes (also in claims 2, 3, 20, 21, 23, 24, 26, 27) |
Sequence identity is central |
| Oligo length 30–50 nt |
Yes (claims 1, 19, 22, 25) |
Yes; injectable claims set 30 nt |
Length helps narrow off-target constructs |
| Uracil optionally thymine |
Yes |
Injectable claims specify thymine bases |
Base-substitution strategy is a design boundary |
| RNase H not activated |
No |
Claim 5 |
Mechanism testing needed only if dependent claim asserted |
| Non-natural backbone/sugar/non-natural linkages |
No |
Claims 6–13 |
Chemistry choice drives dependent claim coverage |
| Morpholino and/or modified phosphates |
No |
Claims 8, 10, 12, 13 |
A key litigation lever in antisense oligo design |
| Conjugates (PEG/polyamine) |
No |
Claims 16–18 |
PEGylation can be determinative for claims 18 and 32–35 |
| Carrier phosphate-buffered saline |
No |
Claim 30 and all injectable claims 32–35 |
Buffer and route can differentiate product coverage |
| Steroid co-administration |
No |
Claim 31 |
Co-therapy can affect infringement for that dependent claim |
| Injectable IV solution format |
No |
Claims 32–35 |
Route and formulation constraints are narrower than method-only claims |
Key Takeaways
- RE47751’s method claims center on inducing dystrophin exon 51 skipping using an antisense oligonucleotide comprising SEQ ID NO: 181 with 30–50 nt length and uracil optionally thymine substitutions, administered with a pharmaceutically acceptable carrier.
- Dependent claims substantially narrow coverage by requiring non-natural backbone features (including optional morpholino), non-natural internucleotide linkages with optional modified phosphate classes, and optionally constraining mechanism (no RNase H activation).
- The most operationally specific coverage is in the injectable intravenous PBS claims (32–35), which lock the embodiment to a 30-nt thymine-fixed SEQ ID NO: 181 morpholino conjugated to PEG, administered in PBS.
- Without priority/term and Orange Book/litigation/regulatory linkage information, exclusivity timing, Orange Book status, Paragraph IV/biosimilar entry, and court challenges cannot be mapped from the provided data.
FAQs
1) What does “comprising SEQ ID NO: 181” mean for possible antisense variant sequences?
It requires the antisense oligonucleotide to include the claimed SEQ ID NO: 181 sequence under a “comprising” standard; base substitutions are bounded by the “uracil optionally thymine” language.
2) Do the claims cover both Duchenne and Becker muscular dystrophy?
Yes. The muscular dystrophy treatment claim (claim 25) includes dependents specifying Duchenne (claim 29) and Becker (claim 28), and the injectable IV claims specify Duchenne (claim 35).
3) Is PEGylation required to fall within RE47751?
PEG is not required for the broadest method claims, but it is required for at least claim 18’s dependent coverage and for the injectable IV claims 32–35.
4) Can an entrant avoid RE47751 by using a different backbone?
Dependent coverage can be avoided by changing backbone and linkage features, but the independent method claims still require the SEQ ID NO: 181 sequence and the uracil/thymine boundary; design-around effectiveness depends on matching those core limitations.
5) What role does the RNase H limitation play?
It is present as a dependent narrowing requirement (claim 5) that can become central if the asserted claims include that limitation.
References
No external sources were provided or cited in the prompt; therefore, no APA reference list can be generated.
