US Patent 6,987,103: Scope, Claim Construction, Expiration and Leukemia Patent Landscape

US Patent 6,987,103 protects a treatment strategy using homoharringtonine in patients with chronic myelogenous leukemia, related myeloproliferative disorders or Philadelphia-chromosome-positive acute lymphoblastic leukemia after resistance or intolerance to STI571, the former development code for imatinib. The patent also covers specified combinations with imatinib, cytarabine, interferon, PEG-interferon, decitabine, troxacitabine and farnesyl-transferase inhibitors.

The patent is a method-of-treatment patent. It does not claim homoharringtonine as a chemical compound, an injectable formulation, a manufacturing process or a pharmaceutical composition. Its commercial relevance depended on enforcing treatment claims against use of homoharringtonine, later developed as omacetaxine mepesuccinate and marketed in the United States as Synribo.

The patent’s practical blocking value has ended. The patent term has expired under the 20-year patent-term framework, and the FDA approval of Synribo occurred after the patent’s effective term had largely run its course.[1][2]

What does US Patent 6,987,103 cover?

The patent covers administration of homoharringtonine to a patient with a specified leukemia who has failed, lost response to or cannot tolerate STI571 therapy.

STI571 is imatinib mesylate, marketed by Novartis as Gleevec. Homoharringtonine is a cephalotaxine alkaloid that inhibits protein synthesis. Its semisynthetic pharmaceutical form is omacetaxine mepesuccinate.

The core elements are:

Claim element	Requirement
Disease	CML, a related myeloproliferative disorder or Ph-positive ALL
Prior treatment	Resistance or intolerance to STI571, generally imatinib
Active treatment	Homoharringtonine
Patient	Subject animal, with a dependent claim specifying a human
Combination options	Imatinib, interferon, PEG-interferon, nucleosides or FTIs
Administration	Subcutaneous, intravenous and, in certain claims, oral administration
Dose	Certain dependent claims recite 0.25 to 5 mg/m² or 2.5 mg/m²
Schedule	Two to 14 days per 28-day cycle in a dependent claim

The scope is narrower than a general claim to treating leukemia with homoharringtonine because the principal treatment claim requires a disease setting associated with STI571 resistance or intolerance.

What are the independent claims in US 6,987,103?

Claim 1: Treatment after imatinib resistance or intolerance

Claim 1 is the principal patient-treatment claim. It requires:

Identifying or selecting an animal with CML, a related myeloproliferative disorder or Ph-positive ALL;
Establishing resistance or intolerance to STI571; and
Administering homoharringtonine.

The claim is not limited to a particular homoharringtonine formulation. It also does not require simultaneous administration with imatinib. Sequential treatment after failed imatinib can fall within the claim if the other limitations are satisfied.

The human-use limitation appears in claim 16, not claim 1. Claim 1 therefore uses the broader “subject animal” language, while claim 16 narrows the subject to a human being.

Claim 7: Ex vivo inhibition of resistant myeloid cells

Claim 7 is an in-vitro or ex-vivo cell-use claim. It requires:

A hyperproliferative myeloid cell resistant to STI571;
Contacting the cell with STI571;
Contacting the cell with homoharringtonine; and
Providing the agents in amounts effective to inhibit proliferation.

This claim is structurally different from the patient-treatment claims. It targets experimental, screening or cell-based treatment methods rather than clinical administration to a human.

The claim text contains “STI5171,” which appears to be a drafting or transcription error for STI571. The same issue appears in other claim text as “ST1571.” Claim construction would likely evaluate these references in the context of the specification and the known identity of STI571 as imatinib, but the typographical issue could create avoidable enforcement disputes.

Claim 8: Sequential treatment followed by combination therapy

Claim 8 requires:

A first course of STI571;
Resistance to or failure of that treatment; and
A second course consisting of homoharringtonine plus STI571.

This claim is narrower than claim 1 because it requires combination treatment with both agents in the second course. It is directed to continuing or reintroducing imatinib while adding homoharringtonine after imatinib resistance.

How do the dependent claims narrow the patent?

The dependent claims create several treatment subgroups.

Claims	Added limitation
2-4	Homoharringtonine combined with another antileukemic agent, either simultaneously or sequentially
5	Detailed imatinib-plus-homoharringtonine regimen after cytogenetic or hematologic response and subsequent failure
6	Cytarabine added to the claim 5 regimen
9	Interferon alpha, nucleosides or an FTI
10	Interferon alpha or PEG-interferon
11-14	Nucleosides, including cytarabine, decitabine and troxacitabine
15	Interferon alpha combined with cytarabine
16	Human patient
17-19	Combination with imatinib, including continued imatinib treatment
20-21	Sequential combination with continued STI571
22	STI571 at 400 to 800 mg daily
23	Homoharringtonine at 2.5 mg/m²
24	Homoharringtonine for two to 14 days per 28-day cycle
25	Human patient under claim 8

Claim 5 is the most operationally specific clinical regimen. It requires an initial imatinib course, a response or partial response, continued or reduced-dose imatinib in certain patients, addition of homoharringtonine at a specified dose range, dose adjustment based on cytopenia or adverse effects, and an optional nucleoside.

The more limitations a claim contains, the smaller the potential infringement population. Claims 1, 7 and 8 are the commercially important claims because they define the basic clinical and cell-based strategies. Claims 5, 6 and 22-24 are more vulnerable to non-infringement where actual dosing, scheduling or treatment sequencing differs.

What treatment methods are protected?

The patent has four principal treatment concepts.

Homoharringtonine after imatinib failure

This is the broadest commercial concept. A patient with CML or a related disorder receives homoharringtonine after resistance or intolerance to imatinib.

Homoharringtonine with imatinib

Claims 17-21 cover combinations in which imatinib is administered simultaneously or sequentially with homoharringtonine. Claim 19 expressly addresses continuation of imatinib from prior treatment.

The wording creates a distinction between:

Adding homoharringtonine while imatinib continues;
Administering both agents simultaneously;
Administering homoharringtonine sequentially after imatinib; and
Reusing imatinib in a second course after resistance.

Homoharringtonine with conventional antileukemic agents

The patent identifies interferon alpha, PEG-interferon, cytarabine, decitabine, troxacitabine and FTIs. These claims reach combinations that were clinically plausible in the treatment of resistant myeloid disease.

Ex-vivo cell inhibition

Claim 7 covers contacting resistant myeloid cells with both STI571 and homoharringtonine. This claim could be relevant to research assays or combination screening, although its commercial value is lower than the clinical claims.

Does the patent cover omacetaxine or Synribo directly?

The patent claims treatment with homoharringtonine. Omacetaxine mepesuccinate is a pharmaceutical form of homoharringtonine and was developed for injectable treatment of resistant or intolerant CML.

The claims do not expressly require the trade name Synribo, omacetaxine mepesuccinate, a particular salt, a particular vehicle or a specific prefilled syringe. A product-level infringement analysis would therefore depend on whether the administered active ingredient is legally treated as homoharringtonine within the claim scope and whether the prescribed use satisfies the resistance, disease and dosing limitations.

The patent does not claim:

Omacetaxine mepesuccinate as a composition;
A stable injectable formulation;
A specific container or delivery device;
A manufacturing process for homoharringtonine;
A method of purifying homoharringtonine; or
A broad treatment of all CML patients.

Those categories would have required separate patent claims.

When did US Patent 6,987,103 lose exclusivity?

US Patent 6,987,103 is expired. Its enforceable life was governed by the patent-term rules applicable to a utility patent filed after June 8, 1995, generally 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment and other statutory calculations.[3]

The patent issued on January 17, 2006. Its term did not extend to the present period. The patent therefore cannot now block an otherwise lawful use of homoharringtonine, omacetaxine or an imatinib-homoharringtonine regimen.

The expiration of this patent does not eliminate later patents covering omacetaxine formulations, dosing schedules, manufacturing processes or approved product uses. It removes only the rights arising from US 6,987,103.

What is the Orange Book status of US 6,987,103?

US 6,987,103 is not a current blocking Orange Book patent for Synribo.

The FDA approved Synribo in October 2012 for adults with chronic-phase or accelerated-phase CML with resistance or intolerance to two or more tyrosine kinase inhibitors.[4] A drug product’s Orange Book listing can include patents covering the approved drug, formulation or method of use, but an expired patent does not provide an active exclusivity barrier.

US 6,987,103 also predates the Synribo approval by several years and does not appear to function as a current listed patent protecting the marketed product. The relevant regulatory distinction is:

Issue	US 6,987,103
Patent type	Method of treatment
Current enforceability	Expired
Current Orange Book blocking effect	None
Product exclusivity	Not created by this patent
Relevance to omacetaxine	Historical and technical, not an active patent barrier
Paragraph IV significance	No current Paragraph IV threat based on this expired patent

FDA approval and patent protection are separate systems. Synribo’s approval did not revive or extend the term of US 6,987,103.

Are Paragraph IV challenges or generic-entry risks affected?

A Paragraph IV certification concerns a listed patent for an approved reference drug. A generic applicant can certify that a listed patent is invalid, unenforceable or will not be infringed.[5]

Because US 6,987,103 is expired, it does not create a current Paragraph IV launch barrier. Any current ANDA litigation concerning omacetaxine would have to involve unexpired Orange Book patents, if any, or other commercial and regulatory barriers.

Potential entry scenarios include:

A generic or authorized-generic injectable omacetaxine product relying on an approved reference product;
A competing product using a different formulation or administration schedule;
Off-label use of an alternative homoharringtonine product;
A new drug application for a different formulation or dosing regimen; or
A product marketed after expiration of later Synribo-related patents.

The residual barriers are more likely to involve manufacturing, clinical development, supply of the active pharmaceutical ingredient, sterility assurance and regulatory approval than US 6,987,103.

Which companies are associated with the commercial patent landscape?

The relevant commercial entities are:

Entity	Role
Novartis	Developer and marketer of imatinib, formerly STI571
ChemGenex Pharmaceuticals	Developer of omacetaxine for resistant CML
Teva Pharmaceutical Industries	Commercial sponsor and marketer of Synribo in the United States
Patent owner or applicant associated with US 6,987,103	The patent record, rather than the drug label, controls ownership and assignment analysis

Imatinib and omacetaxine occupy different competitive positions. Imatinib is a BCR-ABL tyrosine kinase inhibitor used earlier in the CML treatment sequence. Omacetaxine is a non-TKI treatment used after resistance or intolerance to multiple TKIs.

The patent’s commercial theory was based on treatment failure in the imatinib era. Modern CML therapy now includes second- and third-generation TKIs, including dasatinib, nilotinib, bosutinib and ponatinib. That evolution reduces the proportion of patients for whom the exact claim 1 or claim 8 sequence is clinically selected.

How strong is the patent estate for the claimed therapy?

The estate is technically focused but legally narrow.

Strengths

Claims are directed to a defined clinical problem: resistance or intolerance to imatinib.
The treatment sequence is clinically intelligible.
Claims cover both homoharringtonine monotherapy after failure and combinations with imatinib.
Dependent claims identify commercially relevant dosing and scheduling.
The claims distinguish patient treatment from ex-vivo cell inhibition.

Weaknesses

The patent does not claim the active compound or product formulation.
“Related myeloproliferative disorder” is broad and may raise scope and written-description issues.
“Effective amount,” “resistance,” “intolerance” and “subject animal” require fact-specific interpretation.
The claim text contains apparent STI571 typographical errors.
The claimed combinations may face obviousness arguments based on known use of imatinib, homoharringtonine and conventional antileukemic agents.
Many dependent claims are narrow enough to avoid infringement through different dosing, sequencing or combination choices.
The patent is expired, eliminating current enforcement value.

The strongest historical claims were likely claims 1 and 8, while the narrow regimen claims offered more precise but less flexible enforcement positions.

What litigation or settlement agreements affect the patent?

No current litigation consequence follows from US 6,987,103 because the patent is expired. The claim text alone does not establish a settlement agreement, license restriction or active infringement case.

Any historical dispute would need to be evaluated through court dockets, assignment records, FDA patent listings and settlement filings. An expired patent cannot support an injunction against future conduct, although historical damages issues can remain relevant only within the applicable statutory limitation period and subject to the facts of a particular case.[6]

Does the patent create biosimilar risk?

No. Omacetaxine is a small-molecule drug, not a biologic subject to the biosimilar pathway under section 351(k) of the Public Health Service Act.

A competing omacetaxine product would generally present a generic or new-drug regulatory issue rather than a biosimilar issue. The product’s botanical or semi-synthetic origin does not convert it into a biologic for FDA pathway purposes.

Key Takeaways

US 6,987,103 claims treatment of imatinib-resistant or imatinib-intolerant leukemia with homoharringtonine.
The main diseases are CML, related myeloproliferative disorders and Ph-positive ALL.
Claims cover monotherapy after imatinib failure, simultaneous or sequential combinations with imatinib and combinations with other antileukemic agents.
Claim 7 is an ex-vivo cell-proliferation claim.
Claim 8 requires a first imatinib course followed by homoharringtonine plus imatinib.
The patent does not claim omacetaxine as a compound, formulation or manufacturing process.
The patent is expired and does not create a current Orange Book or Paragraph IV barrier.
Omacetaxine is not subject to biosimilar regulation.
Any current patent risk would arise from later product, formulation, dosing, manufacturing or use patents, not from US 6,987,103.

FAQs About US Patent 6,987,103

Is US 6,987,103 still enforceable?

No. The patent has expired under the applicable 20-year utility-patent term framework.

Does US 6,987,103 cover Synribo?

It covers treatment methods using homoharringtonine that can overlap with treatment using omacetaxine, the active pharmaceutical form marketed as Synribo. It does not claim the Synribo formulation or trade product itself.

Does the patent cover imatinib-resistant CML treated with omacetaxine alone?

Potentially, if the treatment satisfies the claim limitations, including the specified disease and resistance or intolerance to STI571. The patent’s expiration eliminates current infringement exposure.

Can a generic company launch omacetaxine after this patent expired?

US 6,987,103 does not prevent launch. A company would still need to address FDA approval requirements, any later unexpired patents and manufacturing or supply constraints.

Are homoharringtonine and omacetaxine the same legal substance?

Omacetaxine mepesuccinate is a semisynthetic pharmaceutical form of homoharringtonine. Whether a particular product falls within a patent claim depends on claim construction, the active ingredient, formulation and use, but this patent is no longer enforceable.

References

United States Patent No. 6,987,103. (2006). Treatment of leukemia with homoharringtonine. United States Patent and Trademark Office.
United States Patent and Trademark Office. (n.d.). Patent term adjustment and patent term calculation.
35 U.S.C. § 154. Patent term.
U.S. Food and Drug Administration. (2012). Synribo (omacetaxine mepesuccinate) prescribing information.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations.
35 U.S.C. § 286. Limitation on damages.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Teva Pharms Intl	SYNRIBO	omacetaxine mepesuccinate	POWDER;SUBCUTANEOUS	203585-001	Oct 26, 2012		DISCN	Yes	No	6,987,103	⤷ Start Trial				TREATMENT OF PATIENTS WITH TYROSINE KINASE INHIBITOR (TKI) RESISTANT OR INTOLERANT CHRONIC MYELOID/MYELOGENOUS LEUKEMIA (CML)	⤷ 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
Austria	451106	⤷ Start Trial
Austria	548041	⤷ Start Trial
Australia	2002337410	⤷ Start Trial
Canada	2459822	⤷ Start Trial
Cyprus	1109799	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 6,987,103

Which drugs does patent 6,987,103 protect, and when does it expire?

Summary for Patent: 6,987,103