US Patent 6,222,025: Scope of Claims, Claim-Chartable Boundaries, and US Landscape Impact

US Patent 6,222,025 claims oligomeric compounds built from one or more monomeric sub-units that carry a phosphorus-containing linking moiety to a nucleotide or oligonucleotide. The patent’s claim scope is defined less by a single drug molecule and more by a modular chemistry set: (i) selectable heteroatoms (O/S), (ii) a tunable “R” substituent space (halo and substituted C1-C6 alkyl families), (iii) multiple “Z” definitions (including fluoro and various chain/aryl-like substituents), and (iv) a broad set of phosphorus linkage types plus end-group/attachment variants (hydroxyl, protected hydroxyl, phosphate/phosphite forms, activated solid support).

The independent claim set you provided is followed by numerous narrowing dependents by heteroatom choice (L = O), Z = F, and degree of polymerization (5–200; 5–50; 10–20). Dependent claims also narrow the phosphorus linking moiety taxonomy to enumerated classes (phosphodiester through phosphoramidate). Another axis is positional control: “plurality of monomeric sub-units … located at preselected positions,” which matters for sequence-specific constructs.

What is the core subject matter being claimed?

1) An oligomeric compound with monomeric sub-units defined by Structure I / II / III

The claims define oligomeric compounds that include at least one monomeric sub-unit of:

Structure I (Claim 1), with:
- X = amino
- R = halo or C1-C6 alkyl or substituted C1-C6 alkyl (substitution includes halo, amino, hydroxyl, thiol, ether, thioether)
- L = oxygen or sulfur
- Z = fluoro or O–R1X1
- R1 = C1–C6 alkyl, C6–C10 aryl, C7–C18 alkaryl
- X1 = H, NH2, or imidazole
- Attachment concept: one of Q1/Q2 is attached via a phosphorus-containing linking moiety to a nucleotide or an oligonucleotide; the other of Q1/Q2 is one of:
- hydroxyl, protected hydroxyl
- activated solid support
- nucleotide, oligonucleotide
- activated phosphate, phosphate
- activated phosphite, phosphite
Structure II (Claim 10), with:
- X = hydroxyl or amino
- R/L/Z attachment framework similar, and the phosphorus-containing linking to nucleotide/oligonucleotide is the same “one of Q1/Q2” concept
Structure III (Claim 17), with:
- X = hydroxyl
- R = halo or C1–C6 alkyl or substituted C1–C6 alkyl (same substitution set)
- L = oxygen or sulfur
- R1 is expanded into a long enumerated list of substituent carbon skeletons and functionalized alkyl-like groups (ethyl through eicosyl, branched alkyl variants, and vinyl/allyl/crotyl/propargyl)
- X1 = H, NH2, or imidazole
- Phosphorus-containing linking again: one of Q1/Q2 attaches to a phosphorothioate oligonucleotide; the other is hydroxyl/protected hydroxyl/activated support/nucleotide/oligonucleotide/activated phosphate/phosphate/activated phosphite/phosphite

2) A second independent claim family that uses a broader formula with Z′

Claims 24 and 32 define an oligomeric compound of “formula” with a flexible terminal/side group definition:

A = hydroxyl or amino
R = halo or C1–C6 alkyl or substituted C1–C6 alkyl (same substitution set)
L = oxygen or sulfur
Z′ = substituted/unsubstituted hydrophobic families:
- substituted C1–C30 alkyl
- substituted/unsubstituted C1–C30 alkenyl
- substituted/unsubstituted C1–C30 alkynyl
- substituted C6–C14 aryl
- substituted C7–C30 aralkyl
- with substitution limited to halo/amino/hydroxyl/thiol/ether/thioether
Q1/Q2 phosphorus connection: one of Q1/Q2 attaches via a phosphorus-containing linking moiety to a nucleotide/oligonucleotide; the other is hydroxyl/protected hydroxyl/activated support/nucleotide/oligonucleotide/activated phosphate/phosphate/activated phosphite/phosphite

This formula family expands “Z” beyond fluoro and O–R1X1 into a broad hydrophobic chain/aryl/alkenyl/alkynyl space.

3) The claimed linkage chemistry is broad by design

Across claims 1 and the later variants, the phosphorus-linking moiety is enumerated (Claim 7, and Claim 14/21/31 in dependent forms). The linking moiety types include:

Claim subset	Linking moiety types explicitly recited
Claim 7 (depends on Claim 1)	phosphodiester, phosphotriester, hydrogen phosphonate, alkylphosphonate, alkylphosphonothioate, arylphosphonothioate, phosphorothioate, phosphorodithioate, phosphoramidate
Claim 14 (depends on Claim 10)	same list as above
Claim 21 (depends on Claim 17)	same list as above
Claim 31 (depends on Claim 24)	same list as above

This breadth matters for infringement analysis: the claim language can read on multiple nucleic-acid conjugation formats that use different phosphorus connectivity patterns.

Where exactly does the claim scope narrow? (Degree of polymerization, heteroatom, Z, linkage class)

1) Degree of oligomerization

The patent uses three explicit polymer-length windows:

Claim	Range recited
Claim 4	5 to 200 sub-units
Claim 5	5 to 50 sub-units
Claim 6	10 to 20 sub-units
Claim 12	5 to 50 sub-units (for Structure II family)
Claim 13	10 to 20 sub-units (for Structure II family)
Claim 19	5 to 50 sub-units (for Structure III family)
Claim 20	5 to 50 sub-units (duplicate as provided)
Claim 28	5 to 200 sub-units (for formula family)
Claim 29	5 to 50 sub-units
Claim 30	10 to 20 sub-units

In practice, these dependent claims create multiple “fallback” positions for enforcement against different oligomer sizes.

2) Heteroatom choice (L = O)

For each major family, there are narrowing dependents that set:

Claim 2: L is O (Structure I)
Claim 11: L is O (Structure II)
Claim 18: L is O (Structure III)
Claim 25: L is O (formula family)

This suggests the specification supports at least oxygen-based and sulfur-based variants, but the patent keeps an oxygen-specific enforcement path.

3) Z-specific narrowing

Two different “Z” tracks appear:

Structure I track:
- Claim 3: Z is F
Formula/Z′ track:
- Claim 26–27: example-specific narrowing where Z is (CH2)n–O–(CH2)m–CH3, with n=2 and m=0

These dependents are important because they define “prototype embodiments” within broader chemical spaces.

How broad is the attachment to nucleotides/oligonucleotides?

1) The Q1/Q2 “one side attaches, the other side is functional” architecture

Claims repeatedly state:

One of Q1 and Q2 is attached via a phosphorus-containing linking moiety to a nucleotide/oligonucleotide.
The other of Q1 and Q2 is one of several endpoint states (hydroxyl, protected hydroxyl, activated solid support, nucleotide/oligonucleotide, activated phosphate/phosphate, activated phosphite/phosphite).

That drafting creates a scope that is not limited to a single end-group identity or a single synthetic stage. It covers:

conjugated end states (nucleotide/oligo on one side)
free functional handles (hydroxyl/protected hydroxyl)
synthetic supports/intermediates (activated solid support)
phosphorylated endpoints (activated phosphate/phosphate; activated phosphite/phosphite)

2) Structure III includes a phosphorothioate-specific constraint

Claim 17 differs from Claim 1/10 in one key way:

“one of Q1 and Q2 is attached via a phosphorus containing linking moiety to a phosphorothioate oligonucleotide.”

This converts one family from generic “nucleotide or oligonucleotide” attachment into a phosphorothioate oligo-specific attachment format, reducing the space of accused embodiments for that particular claim path.

What is the legal “unit of infringement” implied by the claims?

1) “At least one sub-unit” versus “plurality of sub-units”

Independent coverage begins at:

“An oligomeric compound comprising at least one monomeric sub-unit of structure I/II/III” (Claims 1/10/17) and later adds:
“having a plurality of monomeric sub-units” with “preselected positions” (Claims 8–9, 15–16, 22–23, 32–33)

A product with only one qualifying sub-unit could still fall within the “at least one” independent claims, while positional specificity dependents target more engineered constructs.

2) Positional control as a secondary claim axis

For example:

Claim 9: plurality of monomeric sub-units located at preselected positions
Claim 16: same concept for Structure II
Claim 23 and Claim 33: same for Structure I/formula

From an enforcement perspective, these dependents help in cases where accused products are oligomeric but not uniformly substituted.

How does the claim structure translate into a practical “claim boundary map”?

The most actionable way to treat this claim set is to model it as four stacked gates:

Gate A: Monomer identity family

Structure I (X = amino; Z includes fluoro or O–R1X1)
Structure II (X = hydroxyl or amino; Z not constrained to fluoro-only)
Structure III (X = hydroxyl; R1 enumerated; attachment to phosphorothioate oligo)
Formula family (A = hydroxyl or amino; Z′ broad C1–C30 chain and aryl space)

Gate B: Backbone heteroatom

L = oxygen or sulfur, with oxygen-specific dependent claims

Gate C: End-group attachment pattern and nucleic-acid linkage

Q1/Q2: one side tethered via phosphorus linking moiety to nucleotide/oligonucleotide
other side: hydroxyl/protected hydroxyl/activated support/phosphate/phosphite/nucleotide/oligo
linking moiety type: from an enumerated list (phosphodiester, phosphotriester, hydrogen phosphonate, etc.)

Gate D: Oligomer length and sub-unit distribution

length windows: 5–200, 5–50, 10–20
positional placement: preselected positions dependents

What does this mean for the US patent landscape (design-arounds, likely overlap, and risk areas)?

1) High overlap risk for modular conjugates to oligonucleotides

Because the claims are drafted around:

an oligomeric scaffold with tunable substituents
broad nucleic-acid attachment via a phosphorus link
explicit allowance for multiple phosphorus chemistries

the risk is not tied to one final drug format. It extends to a class of nucleic-acid conjugate chemistries where an oligomeric module is attached through phosphorous moieties.

2) Design-around leverage points

Under typical infringement analysis, the main “avoidance levers” would be:

Avoid the monomer family definitions (Structure I vs II vs III vs formula family)
- especially “Z” constraints in the Structure I branch (including F or O–R1X1)
- and the phosphorothioate oligonucleotide constraint in the Structure III branch
Use phosphorus linking chemistry outside the enumerated list (if possible)
- the dependent claims enumerate specific phosphorus linkage types; a strict reading could focus on those types
Change the Q1/Q2 attachment logic (what counts as “via a phosphorus containing linking moiety to a nucleotide or oligonucleotide”)
Adjust oligomer length outside claimed windows (for dependent claims)
- note: independent claims in your excerpt do not appear to impose the 5–200 limit explicitly for Claim 1/10/17; the range limitations are in dependent claims you provided (Claims 4–6, 12–13, 19–20)

3) Positional substitution can be a narrowing litigation battleground

Products with oligomeric substitution patterns that are random rather than “preselected positions” are more likely to attack dependents (Claims 9, 16, 23, 33). If a product uses defined placement, those dependents become stronger.

4) Oxygen vs sulfur (L) can be a practical differentiation point

The existence of oxygen-specific dependents (L = O) implies sulfur variants exist in embodiments. If a product’s monomer incorporates sulfur where the claim requires oxygen, that can reduce overlap for oxygen-only dependents, though not necessarily the broader “L is oxygen or sulfur” independent language.

What is the claim set’s enforcement “ladder”?

This patent reads like a ladder of coverage:

Independent scaffold claims (Claims 1, 10, 17, 24) with broad nucleic-acid attachment and tunable side groups.
Dependent narrowing for:
- oxygen-only heteroatom (L = O)
- Z = F (Structure I) and specific Z-chain example (formula family)
- oligomer length windows
- enumerated phosphorus linking moiety types
Dependent narrowing for positional substitution (preselected positions)

That structure is designed to preserve coverage across product variants:

different monomer substitution options
different nucleic-acid linkage chemistries
different oligomer sizes
different substitution mapping strategies

Key Takeaways

US 6,222,025 claims oligomeric, nucleic-acid-conjugated compounds defined by modular monomer sub-unit structures (Structure I/II/III and a broad formula family).
Scope is driven by four core knobs: monomer identity (X/R/L/Z or A/R/L/Z′), heteroatom L (O/S), phosphorus linkage class to nucleotide/oligonucleotide, and oligomer length/substitution pattern.
The phosphorus linking moiety is broad through an enumerated list (phosphodiester, phosphotriester, hydrogen phosphonate, alkyl/aryl phosphonate and phosphonothioate variants, phosphorothioate/dithioate, phosphoramidate).
Dependent claims create a practical enforcement ladder: L = O, Z = F, specific Z chain example, oligomer length (5–200; 5–50; 10–20), and preselected sub-unit positions.
Landscape risk is concentrated in oligonucleotide conjugate chemistries using phosphorus-based linkage to modular oligomeric subunits, with specific sub-branches for phosphorothioate oligonucleotides (Structure III) and oxygen-only embodiments (L = O dependents).

FAQs

Does US 6,222,025 claim a specific drug molecule?
No. It claims oligomeric compounds defined by modular monomer sub-units and phosphorus-linked attachment to nucleotide/oligonucleotide payloads.
What is the most important claim element for infringement analysis?
The combination of (i) monomer sub-unit definition (Structure I/II/III or the formula family) plus (ii) the phosphorus-containing linking moiety attachment to a nucleotide or oligonucleotide, while respecting (iii) L (O/S) and (iv) oligomer length/position rules in dependents.
Can a product that uses a phosphorothioate oligonucleotide still fall under the claims?
Yes, but with structure-dependent effects. Claim 17 explicitly ties the attachment to a phosphorothioate oligonucleotide.
Which dependents most directly support size-based enforcement?
Claims limiting sub-unit count: 5–200 (Claims 4 and 28), 5–50 (Claims 5, 12, 19, 20, 29), and 10–20 (Claims 6, 13, 30).
What is the litigation relevance of “preselected positions”?
It narrows dependent claims for engineered substitution patterns. Products with non-defined or random placement are less likely to satisfy those dependents.

References

[1] US Patent 6,222,025 claim text (as provided in prompt).

PCT Information
PCT Filed	March 06, 1996	PCT Application Number:	PCT/US96/03174
PCT Publication Date:	September 12, 1996	PCT Publication Number:	WO96/27606

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	327244	⤷ Start Trial
Australia	5359496	⤷ Start Trial
Canada	2214535	⤷ Start Trial
Germany	69636160	⤷ Start Trial
European Patent Office	0813539	⤷ Start Trial
Japan	2001097994	⤷ Start Trial
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Details for Patent: 6,222,025

Summary for Patent: 6,222,025