United States Patent 7,511,131 (Antisense Oligonucleotides): Scope, Claim Boundaries, and Landscape

US Drug Patent 7,511,131 claims a defined antisense oligonucleotide family built around (i) a specific “target” sequence defined by SEQ ID NO:3 and (ii) a specific “lead” sequence defined by SEQ ID NO:247, with layered chemistry: phosphorothioate backbones, 2’-O-methoxyethyl (2’-MOE) sugars, bicyclic sugar variants, and 5-methylcytosine (plus optional chimeric arrangements and salt forms). The claims also extend into formulations, including penetration enhancers (notably capric acid and lauric acid) and combination therapy with anti-inflammatory agents.

Because the claim language is heavily structural and composition-based (sequence-anchored plus modification-anchored), the enforceable scope is concentrated in products that match the claimed sequences and modification patterns, or that fall within the claim’s dependent refinements.

What does claim 7,511,131 protect at the molecule level?

1. Core oligonucleotide scope (SEQ ID NO:247 anchored)

Independent claim 1 covers:

Antisense oligonucleotide length: 20 to 30 nucleobases
Sequence requirement: nucleobase sequence comprising the nucleobase sequence of SEQ ID NO:247
Optional acceptable variants: pharmaceutically acceptable salt forms

Dependent narrowing then locks major chemistry choices:

Claim 2: explicitly 20 nucleobases with nucleobases consisting of the SEQ ID NO:247 sequence
Claim 3-4: at least one modified internucleoside linkage, specifically phosphorothioate as a dependent example
Claim 5-7: at least one modified sugar moiety, specifically 2’-O-methoxyethyl or bicyclic sugar
Claim 8-10: chimeric design with 2’-deoxynucleotides flanked by nucleotides bearing modified sugar moieties
- dependent claim 9: 2’-O-methoxyethyl flanks
- dependent claim 10: bicyclic flanks
Claim 11-12: at least one modified nucleobase, including 5-methylcytosine
Claim 13-14: salt forms (dependent example: sodium salt)

Scope implication: Claim 1 is broad on length and allows the SEQ ID NO:247 segment to be “comprising,” which can include sequence variants that keep SEQ ID NO:247 as a component. However, many downstream dependent claims convert “comprising” into strict “consisting of” (notably Claim 2 and Claim 16), and the most enforceable subsets are those with full-length and fully specified chemistry.

Is there a fully specified “commercially actionable” sequence example?

2. A highly specific embodiment (Claim 16)

Claim 16 defines a full 20-nucleotide molecule with multiple explicit chemical constraints:

Length: 20 nucleotides
Sequence anchor: “sequence as set forth in SEQ ID NO:247”
Base modification: 5-methylcytosine at nucleobases 2, 3, 5, 9, 12, 15, 17, 19, 20
Backbone: every internucleoside linkage is phosphorothioate
Sugar pattern (chimeric architecture):
- nucleotides 1-5 are 2’-O-methoxyethyl
- nucleotides 6-15 are 2’-deoxynucleotides
- (nucleotides 16-20 are part of the “2’-O-methoxyethyl” group under the claim’s structure description; the claim language explicitly states nucleotides 16-20 are 2’-MOE in the same sentence as nucleotides 1-5 and 16-20)
Optional variant: pharmaceutically acceptable salt form

Claims 17-18 further specify the salt:

Claim 18: salt is sodium

Scope implication: Claim 16 creates a narrow, map-like claim boundary. A product that deviates in any of the following is outside the claim: (i) exact 20-mer identity tied to SEQ ID NO:247, (ii) the exact 5-methylcytosine position set, (iii) “all linkages phosphorothioate,” (iv) sugar segmentation. This is the kind of claim that can support clean infringement analyses for fixed-sequence antisense products.

Does the patent also protect antisense that binds a distinct target region?

3. SEQ ID NO:3 fully complementary binding claims

Independent claim 20 protects a different antisense family defined by binding geometry:

Length: 12 to 30 nucleobases
Complementarity: “fully complementary to SEQ ID NO:3”
Hybridization specificity: hybridizes to the range of nucleotides 3230-3287 as set forth in SEQ ID NO:3
Optional variant: salt forms

Dependent claims:

Claim 21: 12 to 20 nucleobases
Claim 22: antisense oligonucleotide
Claim 23-24: at least one modified internucleoside linkage, specifically phosphorothioate
Claim 25-27: at least one modified sugar moiety, specifically 2’-O-methoxyethyl or bicyclic sugar
Claim 28-30: chimeric oligonucleotide with 2’-deoxynucleotides flanked by modified-sugar nucleotides
- dependent examples for sugar type: 2’-O-MOE or bicyclic
Claim 31-32: at least one modified nucleobase; specifically 5-methylcytosine
Claim 33-34: salt forms; specifically sodium
Claim 35: formulation with pharmaceutically acceptable carrier/diluent

Scope implication: Claim 20 is a functional “target-binding” claim. In practice, it can capture products that differ in sequence length (within 12-30) so long as they are fully complementary to SEQ ID NO:3 and bind nucleotides 3230-3287. The claim is therefore broader than the SEQ ID NO:247-driven set in terms of accommodating sequence length variations, but narrower because it imposes full complementarity to a specific target RNA/DNA definition and a defined binding window.

What structural format does claim 43 impose?

4. Gap-wing architecture with explicit wing chemistry (Claim 43)

Claim 43 (dependent on claim 42) defines a specific 20-mer architecture:

Length: 20 nucleobases (Claim 42)
Structure: a gap segment flanked by 5’ wing segment and 3’ wing segment
- gap segment: “gap segment of ten linked 2’-deoxynucleosides”
- wings: “five linked nucleosides” on each side
Wing sugar modification: “each nucleoside of each wing segment comprises a 2’-O-methoxyethyl sugar modification”
Backbone: “each internucleoside linkage is a phosphorothioate linkage”
Further dependent features: modified nucleobase and modified cytosine sub-sets:
- Claim 44: at least one modified nucleobase
- Claim 45: modified cytosine is 5-methylcytosine
- Claim 46: each cytosine is 5-methyl cytosine

Scope implication: This locks a specific antisense design pattern: phosphorothioate throughout, 2’-MOE in the flanks, deoxy in the gap, plus optionally full cytosine methylation. It is consistent with many therapeutic antisense chemistries used for potency and nuclease resistance, but enforceability here depends on whether a candidate product matches this exact pattern and sequence.

What does the claims set cover for formulations?

5. Carrier/diluent formulations

Claim 15: formulation with antisense oligonucleotide (claims 1-14) + pharmaceutically acceptable carrier/diluent
Claim 19: formulation with antisense oligonucleotide (claims 16-18) + carrier/diluent
Claim 35: formulation with antisense compound (claims 20-34) + carrier/diluent
Claim 39-41: adds anti-inflammatory agents in combination formulations
- Claim 40-41: “further comprising at least one additional pharmaceutically active material” with anti-inflammatory agent; claim 41 specifies anti-inflammatory agent under claim 19 baseline

6. Penetration-enhanced formulations (oral and non-oral)

Claim 36: formulation comprising antisense oligonucleotide of claim 1 + penetration enhancer
Claim 37: penetration enhancer is capric acid or lauric acid
Claim 47: oral formulation comprising antisense compound of claim 20 + diluent/carrier
Claim 48-49: oral formulation includes penetration enhancer; enhancer is capric acid or lauric acid
Claim 56-57: formulation comprising antisense oligonucleotide of claim 16 + penetration enhancer (capric acid or lauric acid)

7. Combination with additional therapeutics

Claim 38: formulation with at least one additional pharmaceutically active material
Claim 39: example anti-inflammatory agent
Claim 50-51: formulation with at least one additional therapeutic agent; claim 51 specifies anti-inflammatory agent (dependent on claim 50)

Scope implication: The formulation layer expands infringement beyond dry drug substance into dosage forms containing specified chemistries plus carriers and enhancers. If a marketed product uses capric acid or lauric acid as a delivery enhancer with the claimed antisense molecule, claim 37 (and parallel oral claims) become central.

What are the outer “bicyclic sugar” boundaries?

6. Bicyclic sugar bridge constraint (n = 1 or 2)

Dependent claims 52-55 define a bicyclic sugar moiety with a specific bridge:

Bridge: “(—CH2—)n group forming a bridge between the 2’ oxygen and the 4’ carbon atoms”
n is 1 or 2
Applied in multiple dependent contexts:
- Claim 52: antisense oligonucleotide of claim 7
- Claim 53: antisense oligonucleotide of claim 10
- Claim 54: antisense oligonucleotide of claim 27
- Claim 55: antisense oligonucleotide of claim 30

Scope implication: This constrains “bicyclic sugar” within the claim set to a specific bridging chemistry. Products using different bicyclic sugar families or different bridge topologies would likely fall outside these dependent claims, but could still fall under higher-level claims that merely require “bicyclic sugar moiety” (without the bridge constraint) if such broader language exists in independent claims in the set.

How broad is claim coverage by “dimension”?

The claims combine three independent dimensions: (A) target/sequence definition, (B) backbone and sugar architecture, and (C) nucleobase and formulation additions.

A. Sequence / targeting dimension

Claim group	What defines the oligo identity	Length	Flexibility
Claim 1-19 (SEQ ID NO:247)	Nucleobase sequence comprising or consisting of SEQ ID NO:247	20-30 (claim 1); 20 (claim 2,16)	“comprising” in claim 1 vs “consisting of” in claim 2/16
Claim 20-35 (SEQ ID NO:3)	Fully complementary to SEQ ID NO:3, hybridizes to nucleotides 3230-3287	12-30 (claim 20)	Sequence and length can vary within the complementarity constraint

B. Chemistry dimension (backbone, sugar, nucleobase)

Feature	Where it is required	Strength of constraint
Phosphorothioate linkages	Claims 3-4 (at least one), 16 (every), 24 (at least one), 43 (each)	Some claims are “at least one,” others are “every/each”
2’-MOE sugar	Claims 6 and 9; claim 16 and 43 wings	Claim 16 and 43 lock pattern
Bicyclic sugar moiety	Claims 7, 10, 27, 30, 52-55	Some dependent claims add strict bridge topology
5-methylcytosine	Claims 12, 16 positions; 45-46	Claim 16 adds exact position set; 45-46 adds “each cytosine”

C. Product form dimension (salt, formulation, enhancers)

Feature	Where it is claimed
Sodium salt	Claims 14, 18, 34, 17-18 dependents
Penetration enhancer	Claims 36-37, 48-49, 56-57
Anti-inflammatory combination	Claims 38-41, 50-51
Oral formulation	Claims 47-49

Patent landscape: practical competitive relevance

1. Where the landscape will concentrate for design-arounds

Given the claim structure, competitors seeking to avoid US 7,511,131 typically have only a few “escape hatches,” each aligned to a different claim dimension:

Target/sequence escape: change the antisense sequence so it no longer contains SEQ ID NO:247 (claim 1/2/16) or no longer is fully complementary to SEQ ID NO:3 binding window (claim 20). This is the cleanest route but also the riskiest for efficacy.
Chemistry escape: keep sequence but alter nucleic acid chemistry so it fails one of the dependent constraints:
- remove phosphorothioate “every/each” requirement (claim 16 or 43), or
- alter sugar type so it is not 2’-MOE in the required positions (claim 16 or 43), or
- alter bicyclic sugar bridge topology (claims 52-55).
Formulation escape: avoid the claimed penetration enhancers (capric acid or lauric acid) in the relevant dosage forms; or avoid combining with anti-inflammatory agents in the manner claimed.

2. Enforcement leverage inside this patent

The strongest enforcement leverage typically comes from the claims that are both:

sequence-complete (e.g., 20-mer “consisting of” SEQ ID NO:247 in claim 2 and claim 16), and
chemistry-complete (e.g., “every internucleoside linkage is phosphorothioate” plus exact sugar and exact 5-methylcytosine positions in claim 16; and “each internucleoside linkage is phosphorothioate” with explicit wing-gap sugar pattern in claim 43).

This matters because many antisense programs share the same general chemistry families (phosphorothioates, 2’-MOE, etc.). Claim 16 and claim 43 are the subsets that reduce ambiguity.

3. How to read “comprising” vs “consisting of” as an infringement filter

“comprising SEQ ID NO:247” (claim 1) is more permissive: an accused product can include additional nucleobases outside the SEQ ID NO:247 segment while still satisfying claim 1.
“consisting of SEQ ID NO:247” (claim 2 and claim 16) is stricter: the accused product’s sequence must match the SEQ ID NO:247 sequence exactly at the full length scope stated.

For portfolio and litigation strategy, this means claim 1 can be asserted against longer analogs that include the core sequence, while claim 16/2 cover the exact therapeutic embodiment more cleanly.

Key Takeaways

US 7,511,131 protects antisense oligonucleotides defined around SEQ ID NO:247 (claims 1-19) and around full complementarity to SEQ ID NO:3 with a binding window at nucleotides 3230-3287 (claims 20-35).
The most operational scope is concentrated in 20-mer embodiments with strict chemistry:
- Claim 16: exact 5-methylcytosine position set, full phosphorothioate backbone, and defined 2’-MOE vs 2’-deoxy sugar segmentation.
- Claim 43: explicit gap-wing architecture with 2’-MOE wings, 2’-deoxy gap, and phosphorothioate throughout.
Formulation claims expand exposure into delivery systems using capric acid or lauric acid as penetration enhancers and into combinations that include anti-inflammatory agents.
Landscape design-arounds will mostly hinge on whether a candidate product changes (i) sequence/target complementarity, (ii) phosphorothioate vs other linkages and sugar pattern, or (iii) delivery enhancer choice and formulation composition.

FAQs

1) What is the patent’s central “sequence” hook?

US 7,511,131 anchors one claim set on nucleobases that comprise or consist of SEQ ID NO:247 (claims 1, 2, 16) and another claim set on antisense that is fully complementary to SEQ ID NO:3 and hybridizes to nucleotides 3230-3287 (claim 20).

2) Which claim is most specific about the chemical composition?

Claim 16. It fixes the 20-nucleotide SEQ ID NO:247-derived sequence, specifies 5-methylcytosine at defined positions, requires phosphorothioate for every linkage, and sets a defined 2’-MOE vs 2’-deoxy sugar pattern.

3) Do the claims require phosphorothioate in all cases?

Not uniformly. Some claims require only at least one modified internucleoside linkage (e.g., claims 3, 23), while others require every/each internucleoside linkage to be phosphorothioate (e.g., claim 16 and claim 43).

4) Are capric acid and lauric acid in-scope only for oral products?

No. They appear in multiple formulation claims, including both general formulations (claims 36-37) and oral formulations (claims 47-49), plus a formulation tied to claim 16 (claims 56-57).

5) Can a company avoid the patent by changing sugar chemistry?

The patent includes dependent constraints that narrow bicyclic sugars (bridge: (CH2)n with n = 1 or 2) and define 2’-MOE placement in specific embodiments. A change that breaks those defined patterns is the type of approach most aligned to avoiding dependent claim coverage, but complete avoidance depends on whether the product still satisfies higher-level claims.

References

[1] User-provided claim text for U.S. Patent 7,511,131 (claims 1-57)

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Kastle Theraps Llc	KYNAMRO	mipomersen sodium	SOLUTION;SUBCUTANEOUS	203568-001	Jan 29, 2013		DISCN	Yes	No	7,511,131	⤷ 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

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2002326481	⤷ Start Trial
Australia	2003237875	⤷ Start Trial
Australia	2003294281	⤷ Start Trial
Canada	2455228	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 7,511,131

Which drugs does patent 7,511,131 protect, and when does it expire?

Summary for Patent: 7,511,131