Details for Patent: 7,407,943

Summary for Patent: 7,407,943

Title:	Antisense modulation of apolipoprotein B expression
Abstract:	Antisense compounds, compositions and methods are provided for modulating the expression of apolipoprotein B. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding apolipoprotein B. Methods of using these compounds for modulation of apolipoprotein B expression and for treatment of diseases associated with expression of apolipoprotein B are provided.
Inventor(s):	Rosanne M. Crooke, Mark J. Graham
Assignee:	Ionis Pharmaceuticals Inc
Application Number:	US10/147,196
Patent Claim Types: see list of patent claims	Use; Dosage form;

United States Patent 7,407,943 Landscape: Scope of Claims, Claim Construction Targets, and US Antisense-as-APOB Patent Estate Impact

US Patent 7,407,943 claims in vivo antisense methods that inhibit apolipoprotein B (ApoB) expression in human cells or tissues using an antisense compound (12-30 nucleobases) that is 100% complementary to SEQ ID NO: 3 (and is not a ribozyme). Dependent claims narrow to common chemistry formats for ApoB antisense drug candidates: 2′-O-modified “gapmer” oligonucleotides (2′-deoxy gap with modified-sugar wings), typical phosphorothioate linkages, and specific nucleobase modifications (including 5-methylcytosine). The patent’s practical scope is driven by three claim pillars: (1) target sequence completeness (100% complementarity to SEQ ID NO: 3), (2) length/window and exclusion rules (12-30 nt, not ribozyme, not start-codon targeted), and (3) chemistry and dosing modality constraints (parenteral, including IV or SC; gapmer structure; enumerated sugar/linkage/base modifications).

Because the claims you provided are already fully transcribed, the analysis below focuses on scope mapping, what is captured vs. designed around, and how this US patent fits into the broader antisense-to-ApoB US freedom-to-operate (FTO) risk profile for LDL/TG/VLDL/lipoprotein(a) lowering indications.

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What does US Patent 7,407,943 claim about ApoB antisense methods in humans?

Core independent claim theme (Claim 1): inhibit ApoB expression in vivo by contacting human cells/tissues with an antisense compound that is:

• 12 to 30 nucleobases long
• 100% complementary to SEQ ID NO: 3
• targeted to a nucleic acid encoding apolipoprotein B
• not a ribozyme

Downstream independent claim theme (Claim 2): decrease serum cholesterol in a human by administering the same type of antisense compound, with outcome-driven dependence:

• Serum cholesterol reductions are not restricted to a single cholesterol class in the independent claim, but later claims specify LDL, VLDL, and total cholesterol.

Claim 3-4 parallel outcome claims: decrease lipoprotein levels and serum triglycerides using the same SEQ ID NO: 3-complementary antisense construct.

Claim pillar 1: “100% complementary to SEQ ID NO: 3” defines the infringement boundary

The infringement boundary is not just “targets ApoB.” It is the more stringent condition that the oligonucleotide is 100% complementary to the sequence in SEQ ID NO: 3.

Practical capture rule

• If an accused antisense oligonucleotide has any mismatch relative to the complement of SEQ ID NO: 3, it does not satisfy the “100% complementary” limitation.

Design-around rule

• Substituting at least one base outside the claimed “100% complement” requirement can avoid literal infringement, but the doctrine-of-equivalents analysis (if asserted) would turn on how strictly SEQ ID NO: 3 complementarity is tied to efficacy/working mechanism in the patent record. On the claim face, the requirement is categorical.

Claim pillar 2: length and “not a ribozyme” narrow modality

• 12-30 nucleobases: this captures typical therapeutic antisense lengths and excludes very short or very long constructs.
• “not a ribozyme”: excludes claimed mechanisms where RNA catalytic activity (self-cleaving) is integral.

Claim pillar 3: parenteral administration and IV/SC are explicit in dependent claims

Claims 13-14, 22-23, 39-40, and 53-54 are modality constraints:

• parenteral administration
• specifically IV or subcutaneous (SC)

If a competitor uses oral dosing, intranasal, topical, or other non-parenteral routes, it may still satisfy the independent method claims if the dependent route limitations aren’t required for infringement. But if a plaintiff selects those narrower dependent claims, route matters.

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How broad are the activity and target-location limitations (start codon exclusion and specific nucleotide windows)?

The patent uses two location concepts:

1. Start codon region exclusion (dependent limitation)
2. Specific nucleotide windows covering large spans of SEQ ID NO: 3

“Not targeted to the start codon region” (dependent)

Claims 10, 19, 36, 50 are all the same idea: the antisense compound is not targeted to the start codon region of SEQ ID NO: 3.

Scope impact

• If a candidate oligo targets the start codon region of the ApoB coding sequence, the narrower dependent claims would not cover it.
• Coverage can still exist under broader independent claims (which do not include the start-codon exclusion), but infringement strategy often prefers narrower claims with fewer prosecution-history estoppel constraints.

Target windows (dependent): nucleotides 1-6530 and 6531-14121

Claims 11-12, 20-21, 37-38, and 51-52 provide two windows:

• nucleotides 1–6530 of SEQ ID NO: 3
• nucleotides 6531–14121 of SEQ ID NO: 3

Scope impact

• These dependent claims do not merely define “within ApoB.” They define which portion of SEQ ID NO: 3 is targeted.
• This is relevant for competitors using alternative transcripts/UTRs or targeting different regions of an ApoB mRNA.

Design-around rule

• Selecting an antisense oligonucleotide region that maps outside these windows could avoid those dependent claims. The independent claims may still be asserted, because they do not contain these window limitations.

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What formulations and oligonucleotide chemistries are protected by US 7,407,943?

The patent’s dependent claims explicitly cover multiple antisense chemistries.

Gapmer architecture (dependent claims 15, 32, 46, 59)

A “gapmer” is required in dependent claims:

• gap segment of linked 2′-deoxynucleotides
• positioned between 5′ and 3′ wing segments

This architecture is consistent with many liver-targeted antisense therapeutics.

Wing modifications (dependent claims 16, 33, 47, 60)

Wing segments include at least one modified sugar selected from:

• 2′-O-methoxyethyl (2′-MOE)
• 2′-methoxy
• 2′-O-alkyl
• bicyclic sugar (a class commonly including constrained sugars)

Specific gapmer lengths (dependent claims 17, 34, 48, 61)

A representative specific embodiment:

• gap segment = 10 2′-deoxynucleotides
• each wing segment = 5 2′-O-methoxyethyl nucleotides

If an accused drug uses a gapmer structure but with different lengths or different wing sugar class, it may fall outside specific dependent claim embodiments, again leaving independent claims (if still SEQ ID NO: 3 complementary) as the main risk driver.

Linkage and base modifications (dependent claims 5-8, 28-31, 42-45, 55-58)

Enumerated modifications include:

• phosphorothioate internucleoside linkage
• 5-methylcytosine as a nucleobase modification
• “at least one modification” in a basket: modified sugar, modified internucleoside linkage, modified nucleobase

Scope impact

• These claims do not require all modifications. They require at least one modification in the specified categories.
• That increases coverage for variants built around the same target sequence.

Antisense oligonucleotide definition (dependent claims 62-65)

Claims 62-65 clarify the antisense compound is an antisense oligonucleotide, aligning with conventional therapeutic chemistry.

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Which lipid endpoints does US 7,407,943 cover: LDL, VLDL, triglycerides, and lipoprotein(a)?

The patent covers lipid-lowering outcomes via layered dependent claims.

Serum cholesterol sub-types (dependent from Claim 2)

Claims 24-26 specify:

• LDL-cholesterol
• VLDL-cholesterol
• total cholesterol

Triglycerides (dependent from Claim 4)

• Claim 4 addresses serum triglycerides.
• Dependent claims narrow chemistry/dosing but keep the TG endpoint.

Lipoprotein levels and lipoprotein(a) (dependent from Claim 3)

• Claim 41 explicitly includes lipoprotein(a) levels.

Endpoint mapping table

Claim cluster	Endpoint(s) explicitly claimed	Limitation type
Claims 2 and 24-26	LDL-C, VLDL-C, total cholesterol	Outcome specification
Claims 4	Serum triglycerides	Outcome specification
Claims 3 and 41	Lipoprotein levels; includes lipoprotein(a)	Outcome specification

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What administration routes are claimed, and does the patent cover IV and SC dosing?

Dependent claims explicitly cover parenteral administration:

• Claims 13-14: Claim 1 dependent
• Claims 22-23: Claim 2 dependent
• Claims 39-40: Claim 3 dependent
• Claims 53-54: Claim 4 dependent

All include:

• IV and SC as examples of parenteral administration.

Infringement posture

• If a competitor uses IV/SC, those dependent claims are reachable.
• If a competitor uses other delivery routes, the dependent claims may be unavailable, but the independent method claims can still be asserted if route is not expressly required at that level.

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How does the claim set translate into a competitor risk matrix for ApoB antisense oligonucleotides?

The patent is “sequence-first.” Chemistry and dosing broaden the method scope but sequence complementarity dominates.

Risk matrix based on core limitations

Variable	How US 7,407,943 treats it	Main design-around lever
Sequence	Must be 100% complementary to SEQ ID NO: 3	Introduce any mismatch vs. the required complement
Length	Must be 12-30 nt	Use outside the range
Not ribozyme	Excludes ribozyme constructs	Keep non-catalytic antisense format
Target region	Dependent: exclude start codon; specify nucleotide windows	Target a different transcript region or outside windows
Chemistry	Dependent: includes gapmer with deoxy gap and modified sugar wings	Use different backbone/format if also trying to avoid dependent embodiments
Modifications	Dependent: phosphorothioate, 5-methylcytosine, modified sugars	Avoid enumerated modification patterns if plaintiff asserts those dependents
Route	Dependent: parenteral; IV/SC	Use a different route if relying on avoiding dependent claims

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What portion of the claims is likely most litigated: independent sequence claims vs dependent chemistry claims?

For litigation strategy in antisense patents, plaintiffs typically prefer the broadest claim with the fewest additional constraints. Here:

• Independent claims 1-4 are the broadest: they require SEQ ID NO: 3 complementarity and antisense (not ribozyme), plus outcome framing for 2-4.
• Dependent claims (5-12, 15-18, 28-34, 42-48, 55-61) are important for narrowing to a competitor’s specific oligomer format when a competitor tries to argue noncompliance on sequence region selection, sugar/linkage/base modifications, or gapmer architecture.

Given your claim text, the most “platform-like” elements (gapmer + modified wings + phosphorothioate) are common across multiple antisense product candidates. That means those dependent claims can map quickly onto market compounds that use similar chemistries, even if the exact SEQ ID NO: 3 complement still controls literal infringement.

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What patent landscape issues arise around US 7,407,943 for antisense ApoB programs?

Even without listing other specific patents (not provided here), the claim structure implies typical landscape dynamics in this technology class:

1. Target-sequence monopolies vs. chemistry “second layer” patents
   • Sequence complementarity to a specific defined sequence (SEQ ID NO: 3) is typically the most defensible and the hardest to design around without changing mechanism.
2. Multiple dependent claims that follow product reality
   • The patent reads like it was drafted to track the chemistry embodiments used in antisense development: modified sugars, phosphorothioate, gapmer structure, and common base substitutions.
3. Large transcript targeting windows
   • The nucleotide window claims (1–6530 and 6531–14121) suggest multiple proof points for how the defined sequence is mapped, potentially supporting enforcement across constructs that differ in exact targeting region but still remain within the defined full target sequence.

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Orange Book status, FDA exclusivity, and Paragraph IV/biosimilar risk for US 7,407,943

No FDA product name, NDA/BLA number, Orange Book listing, or exclusivity data is present in the provided input, and those items cannot be derived solely from the claim text. Under your constraints, this analysis does not supply those missing factual records.

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Key Takeaways

• US 7,407,943 is an antisense-to-ApoB method patent where the dominant infringement requirement is 100% complementarity to SEQ ID NO: 3 for a 12-30 nt antisense compound that is not a ribozyme.
• Dependent claims broaden coverage to common therapeutic design choices: gapmer oligonucleotides with 2′-deoxy gaps flanked by modified-sugar wings (including 2′-O-methoxyethyl), phosphorothioate linkages, and 5-methylcytosine.
• The patent includes outcome sub-claims for LDL-C, VLDL-C, total cholesterol, serum triglycerides, lipoprotein(a).
• Dependent limitations on parenteral route (IV/SC) and target-region constraints (start codon exclusion; nucleotide windows) create additional claim paths for litigation where a competitor matches the exact sequence chemistry or dosing format.

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FAQs

1. Does US 7,407,943 require the antisense oligonucleotide to be exactly 20 nucleobases?
   No. The independent claims require 12-30 nucleobases; “20 nucleobases” appears as a dependent limitation.

2. Is targeting the ApoB start codon allowed under the patent?
   The start codon exclusion is in dependent claims. Independent coverage, as written, is not limited by start codon exclusion.

3. What antisense format does the patent cover most specifically?
   It most specifically covers a gapmer with a 2′-deoxy gap and modified-sugar wings in the dependent claims.

4. Can a phosphorothioate-free oligonucleotide avoid dependent claim coverage?
   If the claim asserted is the dependent phosphorothioate basket, a phosphorothioate-free linkage could avoid that dependent limitation. Independent claims still hinge on 100% complementarity to SEQ ID NO: 3.

5. Is lipoprotein(a) lowering included?
   Yes. Claim 41 explicitly covers lipoprotein(a) levels under the lipoprotein-level method claim.

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References

1. United States Patent 7,407,943 (claims as provided in prompt).

Drugs Protected by US Patent 7,407,943

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate

International Family Members for US Patent 7,407,943

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2002326481
Australia	2003237875
Australia	2003294281
Canada	2455228