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Patent landscape, scope, and claims: |
US Patent 6,987,103: Scope, Claim Boundaries, and US Landscape for Homoharringtonine + STI571 (Imatinib) in STI571-Resistant CML
US Patent 6,987,103 claims treatment and combination regimens using homoharringtonine in STI571 (imatinib)-resistant or -intolerant CML (and specified related leukemias), plus in vitro inhibition of proliferation of STI571-resistant hyperproliferative myeloid cells. The claim center of gravity is (i) selecting patients with demonstrated resistance/intolerance to STI571, and (ii) introducing homoharringtonine alone or in combination (including with STI571 and with additional antileukemic agents, including nucleosides such as cytarabine and decitabine, and agents such as interferon alpha and FTIs).
Below is a structured mapping of claim scope, infringement-sensitive boundaries, and the US patent landscape implications for freedom-to-operate (FTO) and product strategy.
What do the independent claims cover in scope?
Claim 1 (independent): Patient selection + homoharringtonine after STI571 resistance/intolerance
Claim 1 covers a method of treating:
- Chronic myelogenous leukemia (CML),
- a related myeloproliferative disorder, or
- Ph-positive acute lymphocytic leukemia (Ph+ ALL),
in a subject animal (later limited to human in dependent claims).
It requires:
- Selecting/identifying an animal with CML/related disorder showing resistance or intolerance to treatment with STI571; and
- Administering homoharringtonine.
Scope implications
- This is not limited to combining homoharringtonine with STI571 in Claim 1. It is satisfied by STI571-resistance/intolerance identification and homoharringtonine administration.
- The “subject animal” is broad in Claim 1, with dependent claims narrowing to humans.
Infringement-sensitive boundary
- If a clinician treats STI571-intolerant/resistant patients with homoharringtonine without STI571 continued and without the “combination” elements added by later dependent claims, Claim 1 still reads.
Claim 7 (independent): Cell-level inhibition of proliferation in STI571-resistant myeloid cells
Claim 7 claims a method for inhibiting proliferation of:
- a hyperproliferative myeloid cell resistant to STI571,
by:
- contacting with STI571 and
- contacting with homoharringtonine,
in amounts effective to inhibit proliferation.
Scope implications
- This is a combination-at-the-cell level claim.
- It is not framed as “in a subject animal,” so it captures laboratory or ex vivo uses where the specific contacting conditions are met.
Claim 8 (independent): Two-course regimen with STI571 then combination homoharringtonine + STI571
Claim 8 is a treatment method that requires:
- A first course of STI571 in animals where the CML/disorder displays resistance and/or intolerance to STI571; then
- A second course consisting of a combination of homoharringtonine and STI571 in an amount effective to inhibit proliferation of myeloid cells.
Scope implications
- This is the most explicit “sequencing” claim tying together STI571-resistance and continuation into the next regimen.
- It is broader than a dosing-specific claim; it requires only a first course and a second course with the defined drug combination.
How do dependent claims narrow dosing, sequencing, and add-on therapy?
Combination with other antileukemic agents (Claims 2–6, 9–15)
- Claim 2: homoharringtonine is combined with one or more other antileukemic agents.
- Claims 3–4: combination timing is specified as:
- simultaneous (Claim 3), or
- sequential (Claim 4).
- Claim 5: sequential add-on described as “addition to existing STI571 therapy” with a defined multi-step operational regimen (a–d, optionally e).
- Claim 9: examples of “other antileukemic agents” include:
- interferon alpha, or
- one or more nucleosides, or
- a farnesyl transferase inhibitor (FTI).
- Claims 10–12: specify interferon alpha / PEG-interferon, nucleosides, and FTI.
- Claims 13–15: nucleosides include:
- cytarabine (Ara-C) and/or
- decitabine and/or
- troxacytabine,
and combinations can include interferon alpha + cytarabine.
Key structural consequence
- The dependent claims can be read as “fallback coverage” if homoharringtonine is used with standard CML adjuncts, including nucleoside analogs (cytarabine/decitabine/troxacytabine) and interferons, or FTIs.
Nucleoside optional add-on in Claim 5 (step e)
Claim 5 includes an optional step (e): administer an oral nucleoside synergistic with homoharringtonine, added simultaneously or sequentially.
Claim 6 locks the nucleoside example to:
- cytarabine, where cytarabine may be added simultaneously or sequentially to homoharringtonine.
Scope implications
- Even when step (e) is optional, Claim 5 is a structured regimen that can be satisfied if the optional step is implemented as described.
Sequencing and dose parameters that create infringement “anchors” (Claims 5, 8, 22–24)
-
Claim 5 operationalizes add-on while maintaining STI571 in partially resistant patients and includes:
- STI571 until complete cytogenetic or at least complete hematologic response is obtained (step a)
- in partially resistant patients: reduce STI571 to 300 to 400 mg daily but do not remove it if complete responses are not achieved or are lost (step b)
- administer homoharringtonine subcutaneously and/or intravenously or/and orally at 0.25 to 5 mg/m2 (step c)
- adjust homoharringtonine dose and/or STI571 dose based on cytopenia/side effects (step d)
- optional step (e) nucleoside addition (described above)
-
Claim 8 requires a first course of STI571 in resistant/intolerant disease then a second course of homoharringtonine + STI571.
-
Claim 22: STI571 dosage is 400 to 800 mg daily.
-
Claim 23: homoharringtonine dose is stated as 2.5 mg2 (the claim text is internally inconsistent in units, but it is still a hard numerical limitation in the claim as written).
-
Claim 24: homoharringtonine for 2 to 14 days per 28-day cycle.
Strategy consequence
- Numeric dosing and cycle-length claims (22–24) matter for product-specific FTO. If a regimen avoids those numeric bands, it may still infringe method claims without those specific limitations, particularly Claim 1 and Claim 8.
What does this mean for infringement risk by real-world treatment patterns?
High-risk clinical patterns that map tightly to Claim 1
- Using homoharringtonine in STI571-resistant or STI571-intolerant CML patients, even if STI571 is not continued.
- Treating related myeloproliferative disorders or Ph+ ALL with homoharringtonine after STI571 resistance/intolerance identification.
Because Claim 1 does not require homoharringtonine + STI571 combination, clinicians cannot rely on discontinuing imatinib alone to avoid coverage.
High-risk patterns for Claim 8 and dependent sequencing claims
- First course of STI571 in resistant/intolerant patients, then switching to a regimen that includes homoharringtonine + continuing STI571 as a second course.
- Regimens that explicitly continue STI571 during or after homoharringtonine introduction.
High-risk lab/ex vivo patterns for Claim 7
- Any proliferation assay or ex vivo protocol that contacts STI571 plus homoharringtonine with STI571-resistant hyperproliferative myeloid cells and targets proliferation inhibition.
How broad is the “other antileukemic agents” coverage?
Claims 2, 5, and 9–15 create a combinatorial claim scaffold:
- “Other antileukemic agents” can include interferon alpha (including PEG-interferon), nucleosides (cytarabine/decitabine/troxacytabine), and FTIs.
- Dependent claims enumerate specific nucleosides and specific pairing examples (e.g., interferon alpha + cytarabine).
Practical read-through
- A product that uses homoharringtonine with an interferon or with a nucleoside analog in STI571-resistant CML is more likely to land inside the claim set than a regimen limited to homoharringtonine alone.
What is the likely US patent landscape structure around this technology?
1) Likely “combination use” clusters
This patent is a classic “method-of-treatment using a known kinase inhibitor plus another cytotoxic/translation inhibitor” family structure:
- imatinib context: STI571-resistant/intolerant disease characterization
- homoharringtonine as added therapeutic
- optional third agents: nucleosides, interferons, FTIs
In the US landscape, technology like this typically sits among:
- early composition-of-matter or known drug patents (homoharringtonine and imatinib era),
- then later-method patents targeting resistance-defined populations and specific sequencing/combo protocols.
2) Likely competitive pressure points
For newer or follow-on competitors, the highest pressure points are:
- resistance-defined selection language (STI571 resistance or intolerance triggers)
- combination with STI571 (explicit in Claim 8 and cell-level Claim 7)
- defined add-on sequencing with STI571 (Claim 5)
- nucleoside adjuncts (Claim 6 and Claim 13 onward)
- dosing-cycle constraints (Claim 22–24)
3) Where “design-arounds” usually fail
- Discontinuing STI571 is a partial design-around only for claims that explicitly require combination. It does not avoid Claim 1.
- Avoiding numeric dosing (e.g., Claim 24 cycle-length) may avoid a dependent numeric claim but still leaves exposure to broader independent claims that lack those numeric restrictions.
Claim-by-claim scope map (quick reference)
| Claim |
Core treatment concept |
Key limitations that control scope |
| 1 |
Treat CML/related/Ph+ ALL in STI571-resistant/intolerant subject animal with homoharringtonine |
Requires STI571 resistance/intolerance identification; homoharringtonine administration |
| 2 |
Homoharringtonine combined with 1+ other antileukemic agents |
Adds combination element |
| 3 |
Homoharringtonine combined simultaneously with other antileukemic agents |
Timing constraint |
| 4 |
Homoharringtonine combined sequentially with other antileukemic agents |
Timing constraint |
| 5 |
Add homoharringtonine to existing STI571 therapy via multi-step regimen (a–d, optionally e) |
Includes STI571 dosing reduction band, homoharringtonine dose band, cytopenia/side-effect adjustment; optional oral nucleoside |
| 6 |
Nucleoside (step e) is cytarabine |
Nucleoside identity limitation; simult/sequential |
| 7 |
Inhibit proliferation of STI571-resistant hyperproliferative myeloid cells by contacting with STI571 + homoharringtonine |
Requires resistance-defined cell population and dual contact |
| 8 |
First course STI571 then second course homoharringtonine + STI571 |
Two-course sequencing and combo requirement |
| 9 |
Other antileukemic agents examples: interferon alpha / nucleosides / FTI |
Narrows by exemplars |
| 10 |
Other agent is interferon alpha or PEG-interferon |
|
| 11 |
Other agent is 1+ nucleosides |
|
| 12 |
Other agent is FTI |
|
| 13 |
Nucleosides: cytarabine/decitabine/troxacytabine |
|
| 14 |
Nucleoside is cytarabine (Ara-C) |
|
| 15 |
Other agent is interferon alpha + cytarabine |
|
| 16 |
Animal is human |
Jurisdictional/clinical narrowing |
| 17–21 |
Combination timing and STI571 continuation tied to claims 2–5 |
Continuation and simultaneous/sequential language |
| 22 |
STI571 dose 400–800 mg daily |
Numeric anchor |
| 23 |
Homoharringtonine dose “2.5 mg2” |
Numeric anchor (as written) |
| 24 |
Homoharringtonine 2–14 days per 28-day cycle |
Numeric anchor |
| 25 |
Animal is human (for claim 8) |
Jurisdictional/clinical narrowing |
Key Takeaways
- Claim 1 creates broad method coverage for STI571-resistant or STI571-intolerant CML/related/Ph+ ALL where homoharringtonine alone is administered, without requiring ongoing STI571.
- Claim 8 and Claim 7 capture the most explicit combo use: homoharringtonine + STI571 in a second-course regimen or in dual-contact cell inhibition.
- Dependent claims expand risk through timing (simultaneous vs sequential), adjunct agent sets (interferons, nucleosides, FTIs), and a detailed add-on regimen (Claim 5) that includes specific dose bands and cycle structure (Claims 22–24).
- Numeric constraints (STI571 400–800 mg daily; homoharringtonine dosing and 2–14 days per 28-day cycle) affect dependent-claim infringement analysis but do not remove exposure to broader independent claims.
FAQs
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Does Claim 1 require combining homoharringtonine with STI571?
No. Claim 1 requires selecting STI571-resistant/intolerant subjects and administering homoharringtonine; it does not require continuing or co-administering STI571 in Claim 1.
-
Which claims explicitly require homoharringtonine + STI571 in the same method?
Claim 7 (cell-contact with both) and Claim 8 (second course combination) are explicit.
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Do the nucleoside-dependent claims cover cytarabine specifically?
Yes. Claim 6 specifies cytarabine as the optional oral nucleoside in step (e), and Claims 13–14 list cytarabine (Ara-C) as a nucleoside option.
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What is the dosing and cycle-length relevance?
Claim 22 fixes STI571 at 400 to 800 mg daily; Claim 24 fixes homoharringtonine dosing duration as 2 to 14 days per 28-day cycle.
-
Is the patient population limited to CML only?
No. The claims cover CML, a related myeloproliferative disorder, and Ph-positive ALL, and they also include a human limitation in dependent claims.
References
[1] US Patent 6,987,103.
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