US Patent 8,859,562: Scope, Claim Construction, Expiration and PARP Inhibitor Patent Landscape
US Patent 8,859,562 covers a treatment method for cancer associated with defective homologous recombination, or HR, in a patient with a familial predisposition to gene-linked hereditary cancer. The claim requires four linked conditions: patient identification, hereditary-cancer predisposition, HR-defective cancer cells, and administration of a PARP-1 inhibitor.
The patent is method-of-use intellectual property. It does not claim a particular PARP inhibitor molecule, formulation, salt, dosage form, manufacturing process, or biomarker assay. Public patent records identify AstraZeneca as the principal patent holder or assignee. The patent term is generally reported to extend to December 8, 2027, subject to any applicable patent-term adjustment or terminal-disclaimer treatment.[1]
What does US Patent 8,859,562 claim?
Claim 1 recites:
A method of treatment of cancer cells defective in homologous recombination, the method comprising:
- identifying a human patient with a familial predisposition to gene-linked hereditary cancer;
- identifying a compound that inhibits PARP-1; and
- administering a therapeutically effective amount of that compound to the patient.
The claim is directed to the treatment of a selected human patient rather than to cancer treatment generally.
Claim element analysis
| Claim element |
Scope and practical meaning |
| Human patient |
The claim requires treatment of a person, not an in vitro assay or animal model. |
| Familial predisposition |
The patient must have a hereditary or familial risk associated with a gene-linked cancer. |
| Gene-linked hereditary cancer |
The hereditary cancer must be connected to a genetic defect or predisposition, such as BRCA-associated cancer. |
| Cancer cells defective in HR |
The tumor must have impaired homologous-recombination repair. |
| Identifying a PARP-1-inhibiting compound |
The compound must inhibit PARP-1. The claim does not require a specific chemical structure. |
| Therapeutically effective amount |
The administered amount must be clinically effective for the claimed treatment. |
| Administration |
The claim requires actual administration, not merely research, testing, or identification of a candidate compound. |
The claim therefore combines a patient-selection limitation with a mechanism-of-action limitation. A product is not within the claim merely because it is a PARP inhibitor. The patented method requires use in the specified hereditary and HR-defective patient population.
How broad is the scope of claim 1?
Claim 1 is chemically broad but clinically narrower than a general PARP-inhibitor treatment claim.
The phrase "a compound which inhibits PARP-1" can encompass multiple chemical classes, including approved PARP inhibitors that inhibit PARP-1. It is not limited on its face to olaparib, niraparib, rucaparib, talazoparib, or any other named molecule.
The claim is constrained by the patient and disease characteristics:
- The patient must have a familial predisposition.
- The hereditary predisposition must be gene-linked.
- The cancer cells must be defective in HR.
- The treatment must involve a PARP-1 inhibitor.
- The compound must be administered at a therapeutically effective amount.
Does the claim require a BRCA1 or BRCA2 mutation?
Not expressly. Claim 1 does not name BRCA1 or BRCA2. It uses broader language covering familial predisposition to gene-linked hereditary cancer.
BRCA1 and BRCA2 are the clearest commercial examples because pathogenic alterations in those genes can produce homologous-recombination deficiency and hereditary breast, ovarian, pancreatic, prostate, and related cancers. Other genes involved in HR repair may also be relevant, depending on the patent specification, claim construction, clinical evidence, and the facts of a particular use.
The absence of an express BRCA limitation makes the claim potentially broader than a claim limited to germline BRCA-mutated disease. At the same time, the phrase "familial predisposition" may limit the claim to a hereditary or familial-risk context and may not encompass every tumor with a somatic HR-repair defect.
What type of patent protection does US 8,859,562 provide?
US 8,859,562 is primarily a method-of-use patent.
It does not appear, based on the stated claim, to provide independent protection for:
- the PARP inhibitor molecule itself;
- a pharmaceutical composition;
- a tablet, capsule, or other dosage form;
- a combination with chemotherapy or immunotherapy;
- a manufacturing process;
- a diagnostic test;
- a specific BRCA mutation;
- a companion diagnostic;
- a dosing schedule; or
- a crystalline or amorphous solid form.
The commercial importance of the patent depends on whether a marketed product is promoted, labeled, prescribed, or otherwise used for the claimed hereditary HR-deficient population.
When does US Patent 8,859,562 expire?
The patent is generally reported to expire on December 8, 2027, based on the underlying priority and patent-term calculations.[1] The effective date should be confirmed against the USPTO Patent Center record and any applicable term-adjustment information.
Exclusivity timeline
| Event |
Date or status |
| Earliest reported priority date |
December 8, 2006 |
| US patent grant |
2014 |
| Patent number |
US 8,859,562 |
| Reported patent expiration |
December 8, 2027 |
| Patent type |
Method of treatment |
| Small-molecule regulatory exclusivity |
Separate from patent term |
| Biosimilar exclusivity |
Not applicable |
The patent expiration date is distinct from FDA regulatory exclusivity. FDA new chemical entity exclusivity, orphan-drug exclusivity, pediatric exclusivity, and any other regulatory period can restrict approval timing independently of patent rights.[2]
What is the Orange Book status of US 8,859,562?
US 8,859,562 has been associated with AstraZeneca's olaparib product, Lynparza, in the FDA Orange Book patent framework.[3] The relevant commercial question is not whether every claim is directed to olaparib. The question is whether the listed patent claims an approved method of using the drug.
A method patent may be listed when it claims an approved use of the drug. The Orange Book listing can therefore create a Paragraph IV certification issue for an ANDA applicant seeking approval before patent expiration.
Orange Book implications
An ANDA applicant referencing Lynparza may need to address listed patents through one of four certifications:
- Paragraph I: no patent information has been submitted.
- Paragraph II: the patent has expired.
- Paragraph III: the applicant will not market until patent expiration.
- Paragraph IV: the patent is invalid, unenforceable, or will not be infringed.
A Paragraph IV notice can trigger patent litigation under the Hatch-Waxman Act if the patent holder files suit within the statutory period.[4]
The presence of US 8,859,562 in the Orange Book does not establish that the patent will survive a validity challenge or that every proposed generic use infringes. It establishes that FDA patent-listing procedures may affect ANDA approval and litigation timing.
How could a generic applicant challenge US 8,859,562?
A generic applicant could use a Paragraph IV certification and challenge the patent on several grounds.
Noninfringement
A proposed generic may argue that its label does not direct treatment of patients with all required characteristics. Potential arguments include:
- the label does not identify a familial predisposition;
- the indication is limited to somatic HR deficiency;
- the label does not require HR-defective cancer cells;
- the product is not labeled for gene-linked hereditary cancer;
- the relevant patient population is not selected using the claimed criteria; or
- the proposed use does not involve the claimed PARP-1 inhibition.
The strength of a noninfringement position would depend heavily on the ANDA label, the FDA-approved indication, promotional materials, prescribing information, and actual prescribing patterns.
Invalidity
Potential invalidity arguments could include:
- lack of written description for the full breadth of all gene-linked hereditary cancers;
- lack of enablement across all PARP-1 inhibitors and all HR-deficient hereditary cancers;
- anticipation by earlier PARP-inhibitor and BRCA research;
- obviousness based on the known relationship between HR repair defects and PARP inhibition;
- indefiniteness in terms such as "familial predisposition" or "defective in homologous recombination"; and
- lack of patentable subject matter, depending on the claim construction and governing case law.
The claim's combination of patient selection and HR deficiency may provide a stronger patentability position than a claim directed to PARP inhibition alone. Its vulnerability may increase if the specification does not adequately support the full breadth of gene-linked hereditary cancers and PARP-1 inhibitors.
Written-description and enablement exposure
Claim 1 is broad across both patient genetics and chemical compounds. A challenger could argue that the specification does not support every compound that inhibits PARP-1 or every hereditary cancer associated with HR deficiency.
The patent holder would likely rely on:
- the biological relationship between HR deficiency and PARP inhibition;
- experimental evidence involving BRCA1 or BRCA2 deficiency;
- the predictability of synthetic lethality in the relevant tumor class;
- disclosures of representative PARP inhibitors; and
- clinical or preclinical evidence linking hereditary HR defects to treatment response.
Which PARP inhibitors may fall within the claim?
The claim is not limited to olaparib. Depending on the scope of the specification and claim construction, it may reach use of other PARP-1-inhibiting agents in the claimed patient population.
| PARP inhibitor |
Product |
Primary sponsor or commercial company |
Potential relevance |
| Olaparib |
Lynparza |
AstraZeneca and Merck |
Direct commercial relevance; the patent has been associated with Lynparza listings. |
| Niraparib |
Zejula |
GSK, originally Tesaro |
Potential method-of-use overlap if used in the claimed hereditary HR-deficient population. |
| Rucaparib |
Rubraca |
Clovis Oncology |
Potential overlap based on patient selection and PARP-1 inhibition. |
| Talazoparib |
Talzenna |
Pfizer, originally Medivation |
Potential overlap in hereditary HR-deficient breast or other cancers. |
| Pamiparib |
Approved in selected jurisdictions |
BeiGene |
Geographic and regulatory relevance outside the United States. |
| Fluzoparib |
Approved in China |
Hengrui |
Relevant primarily to non-US patent landscapes. |
This patent does not automatically block all competing PARP inhibitors. Infringement requires practice of the claimed method in the United States. A product may have separate freedom-to-operate issues under compound, formulation, dosage, combination, or other method patents.
How does US 8,859,562 compare with olaparib compound patents?
The patent should be analyzed as one layer of a broader olaparib estate.
| IP layer |
Typical subject matter |
Business effect |
| Compound patents |
Olaparib chemical structure and related compounds |
Can block sale of the active ingredient. |
| Salt and solid-form patents |
Crystalline forms, salts, polymorphs |
Can restrict specific commercial versions. |
| Formulation patents |
Tablets, compositions, excipients, release profiles |
Can affect generic product design. |
| Method-of-use patents |
BRCA-mutated, HR-deficient, ovarian, breast, pancreatic, or prostate cancer treatment |
Can delay or narrow generic launch. |
| Combination patents |
Olaparib with endocrine therapy, immunotherapy, antiangiogenic agents, or chemotherapy |
Can protect specific regimens. |
| Manufacturing patents |
Synthetic intermediates and processes |
Can create supply-chain and process-design barriers. |
| Regulatory exclusivity |
FDA exclusivity periods |
Can delay approval independently of patents. |
US 8,859,562 is most important where compound protection is approaching expiration but the approved indication continues to overlap with the claimed hereditary HR-deficient population.
What formulation patents protect PARP inhibitors?
Formulation patents are separate from US 8,859,562. They may cover:
- immediate-release tablets;
- particular excipient combinations;
- particle-size distributions;
- solid dispersions;
- polymorphic forms;
- salt forms;
- stability-enhancing compositions; and
- specified dissolution or bioavailability profiles.
A generic applicant can sometimes avoid a formulation patent by using a different excipient system or solid form. That strategy does not necessarily avoid a method-of-use patent if the generic label still encourages the claimed treatment.
For Lynparza, the relevant patent estate has included product, formulation, and use-related patents. A complete launch analysis must examine every active Orange Book listing, not only US 8,859,562.[3]
What manufacturing and IP barriers affect generic launch?
The patent is not a manufacturing patent, so it does not directly block production of a non-infringing PARP inhibitor. Manufacturing barriers may still arise from separate rights covering:
- protected synthetic routes;
- intermediates;
- impurity controls;
- polymorph selection;
- tablet manufacture;
- process scale-up;
- analytical methods; and
- supplier-specific starting materials.
For an ANDA applicant, the commercial launch question has at least three independent parts:
- Can the applicant manufacture the active ingredient and finished product without infringing process or formulation patents?
- Can it obtain FDA approval under the proposed label?
- Can it launch without infringing listed method-of-use patents?
What is the biosimilar risk for US 8,859,562?
There is no conventional biosimilar risk. PARP inhibitors are small-molecule drugs regulated through the ANDA pathway, not biological products regulated through the biosimilar pathway.
The relevant competitive threats are:
- generic olaparib;
- authorized generic olaparib;
- competing branded PARP inhibitors;
- label carve-outs;
- post-patent price erosion; and
- generic entry following Paragraph IV litigation or settlement.
What litigation and settlement issues matter?
A Paragraph IV challenge to US 8,859,562 could trigger a Hatch-Waxman infringement action and a stay of FDA approval for up to 30 months, subject to statutory exceptions.[4]
The principal litigation issues would likely include:
- whether the generic label induces use in hereditary HR-deficient cancer;
- whether "familial predisposition" is satisfied by the proposed indication;
- whether the generic product is a PARP-1 inhibitor within the claim;
- whether HR deficiency is required to be clinically tested or may be inferred from the diagnosis;
- whether the claim is enabled across the full patient population;
- whether the patent is obvious in light of BRCA/PARP literature; and
- whether any settlement permits an authorized or licensed generic launch before December 2027.
Public settlement terms can include delayed-entry dates, licenses, authorized-generic commitments, manufacturing restrictions, or covenants not to sue. The commercial value of a settlement depends on whether the entry date precedes, matches, or follows expiration of the compound and formulation patents.
What is the competitive landscape for PARP inhibitors?
The principal US competitive products are Lynparza, Zejula, Rubraca, and Talzenna. Competition depends on indication, biomarker requirement, combination regimen, line of therapy, safety profile, and patent runway.
Olaparib has had the broadest commercial profile, with approvals spanning ovarian, breast, pancreatic, and prostate cancer settings. Talazoparib has been important in germline BRCA-mutated breast cancer. Niraparib and rucaparib have competed in ovarian and related tumor indications, although their commercial positions have changed with clinical-label developments and corporate restructuring.
A patent claim directed to hereditary HR-deficient cancer can affect multiple products in theory. In practice, enforcement is most consequential when:
- the product label expressly identifies hereditary or BRCA-linked disease;
- the product is marketed for HR-deficient tumors;
- the patent is listed against that product; and
- the competing product has no practical label carve-out.
How strong is the patent estate?
US 8,859,562 has meaningful commercial scope but should not be treated as a complete barrier to PARP-inhibitor competition.
Strengths
- It is not limited to a single chemical compound.
- It targets a clinically important biomarker population.
- It covers the biological relationship between HR deficiency and PARP-1 inhibition.
- It may reach multiple PARP-1 inhibitors.
- It can be relevant to ANDA litigation if listed for an approved method.
Vulnerabilities
- The claim requires a familial predisposition, which may exclude some purely somatic HR-deficient cancers.
- The scope of "gene-linked hereditary cancer" may be disputed.
- "Defective in homologous recombination" may raise claim-construction and proof issues.
- Broad coverage of PARP-1 inhibitors creates enablement and written-description exposure.
- A generic may seek a label carve-out that avoids the claimed use.
- The patent does not protect the active ingredient, formulation, or manufacturing process by itself.
The patent is strongest when the competing product's label expressly directs treatment of patients with inherited BRCA or another hereditary HR-repair defect. It is weaker where the proposed product is approved only for an indication that does not require hereditary predisposition or HR deficiency.
Key Takeaways
- US 8,859,562 is a method-of-treatment patent covering PARP-1 inhibition in patients with hereditary, gene-linked cancer associated with HR-defective tumor cells.
- Claim 1 is chemically broad but patient-population limited.
- The claim is not expressly restricted to BRCA1 or BRCA2, although BRCA-associated cancers are the central commercial example.
- The patent does not claim olaparib, a formulation, a dosage form, or a manufacturing process.
- The reported expiration date is December 8, 2027.
- The patent has been associated with AstraZeneca's Lynparza Orange Book estate.
- Paragraph IV litigation would likely focus on induced infringement, hereditary-predisposition requirements, HR-deficiency proof, obviousness, written description, and enablement.
- Biosimilar law is not relevant because PARP inhibitors are small molecules.
- Generic launch risk depends on the full Orange Book estate, not this patent alone.
- The patent has its greatest leverage against labels that expressly direct treatment of inherited BRCA or other hereditary HR-repair defects.
Frequently Asked Questions
Does US 8,859,562 cover all PARP inhibitors?
No. It does not claim every PARP inhibitor as a product. It covers a treatment method using a compound that inhibits PARP-1 in the specified hereditary HR-deficient cancer setting.
Can a generic olaparib launch before December 2027?
Potentially, but only if it avoids or defeats relevant patent rights, obtains a license or settlement, uses an approved label carve-out, or otherwise establishes a legally permissible launch position. US 8,859,562 is only one part of the analysis.
Does a somatic BRCA mutation satisfy the patent claim?
Not necessarily. The claim requires a familial predisposition to gene-linked hereditary cancer. A purely somatic mutation, without a hereditary or familial component, may not satisfy that limitation.
Does the claim require a diagnostic test confirming HR deficiency?
The stated claim requires identifying a patient whose cancer cells are defective in HR, but it does not expressly prescribe a particular diagnostic assay. The method of establishing that fact would be relevant to infringement and claim construction.
Does patent expiration eliminate all Lynparza exclusivity?
No. Patent expiration affects only the rights conveyed by that patent. Separate compound, formulation, dosage, combination, process, regulatory-exclusivity, and other method patents may affect generic approval or launch.
References
- United States Patent and Trademark Office. (2014). US Patent No. 8,859,562, methods of treating cancer using a PARP inhibitor.
- U.S. Food and Drug Administration. (2024). Drugs@FDA: FDA-approved drugs and regulatory exclusivity information.
- U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
- U.S. Food and Drug Administration. (2024). Abbreviated new drug application approvals and patent certifications under the Hatch-Waxman Act.
