US Patent 8,071,579: PARP Inhibitor Treatment of Homologous-Recombination-Deficient Cancers
US Patent 8,071,579 covers a biomarker-directed method of treating cancer with a PARP inhibitor after identifying deficiency in homologous-recombination DNA double-strand-break repair. Its central commercial concept is the synthetic-lethal treatment of BRCA1- or BRCA2-deficient tumors with PARP inhibition. The claims are not limited to olaparib, breast cancer, ovarian cancer, or germline BRCA mutations.
The patent was assigned to Cancer Research Technology Limited and originated from research associated with the Institute of Cancer Research, KuDOS Pharmaceuticals and Professor Alan Ashworth’s group. AstraZeneca acquired KuDOS in 2005 and commercialized olaparib, the principal drug associated with the patent family.
What does US Patent 8,071,579 claim?
The independent claim requires four core elements:
- A cancer patient or individual.
- Identification of a cancer cell as deficient in homologous-recombination-dependent DNA double-strand-break repair relative to normal cells.
- Administration of a PARP inhibitor.
- Treatment of cancer.
The claim is a treatment-selection claim, not a composition-of-matter claim. It does not claim the PARP inhibitor molecule itself, a BRCA mutation as such, or a specific formulation.
| Claim |
Subject matter |
Practical limitation |
| 1 |
Treating HR-deficient cancer with a PARP inhibitor |
Requires patient selection based on HR repair deficiency |
| 2 |
Measuring HR-dependent DNA repair activity |
Requires functional assessment |
| 3 |
Measuring Rad51 nuclear foci after DNA damage or PARP inhibition |
Defines a specific functional assay |
| 4 |
Detecting mutations or polymorphisms in HR pathway genes |
Covers genomic biomarker testing |
| 5 |
Reduced or abrogated HR repair relative to normal cells |
Broad functional deficiency language |
| 6 |
BRCA1- or BRCA2-deficient cancer |
Expressly covers BRCA-associated tumors |
| 7 |
Homozygous BRCA1 or BRCA2 mutation |
Covers biallelic mutation states |
| 8 |
Heterozygous BRCA1 and/or BRCA2 mutation |
Broadens the claim to heterozygous states |
| 9 |
PARP inhibitor that is a phthalazin-1(2H)-one |
Important for olaparib-type chemical structures |
| 10 |
Comparing HR repair activity with normal cells |
Adds a comparative diagnostic requirement |
| 11 |
HR pathway deficiency relative to normal cells |
Repeats and reinforces the biomarker limitation |
What is the commercial scope of the patent?
The broadest commercial scope is claim 1. A product sponsor or healthcare provider could face infringement questions where the treatment protocol includes:
- Testing a tumor for HR repair deficiency;
- Selecting the patient because of that deficiency; and
- Administering a PARP inhibitor.
The patent does not require that the deficiency result from BRCA1 or BRCA2. Potentially relevant defects include alterations affecting RAD51, PALB2, RAD51C, RAD51D, ATM, CHEK2, BRIP1 and other components of homologous recombination. The claims, however, require that the cancer actually be deficient in HR-dependent DNA double-strand-break repair. A gene alteration alone may not establish infringement if it does not produce the claimed functional deficiency.
The patent also does not expressly require:
- A particular tumor type;
- A germline mutation;
- A somatic mutation;
- A particular PARP isoform;
- A specific treatment dose;
- A specific treatment line;
- A companion diagnostic approved by the FDA; or
- A particular level of PARP trapping activity.
How do the dependent claims affect infringement risk?
BRCA1 and BRCA2 claims
Claims 6 through 8 narrow the invention to BRCA-associated deficiency. Claim 6 covers BRCA1- or BRCA2-deficient cancer generally. Claims 7 and 8 distinguish homozygous and heterozygous mutation states.
The inclusion of heterozygous mutations in claim 8 is commercially significant but legally more vulnerable than claims requiring complete loss of function. A heterozygous mutation does not necessarily establish that the tumor is HR-deficient. The relevant question is whether the tumor has a functional repair defect, often caused by loss of the remaining wild-type allele, epigenetic silencing, or another second-hit event.
Rad51-foci claim
Claim 3 is directed to a functional assay based on Rad51 foci formation in the nucleus following DNA damage or PARP inhibition. Rad51-foci testing can measure the ability of tumor cells to mount a homologous-recombination response.
This claim is narrower than claim 1 because it requires a specified assay. A diagnostic platform that uses a different HR-deficiency assay may fall outside claim 3 while remaining potentially relevant to claim 1 or claim 4.
Genomic testing claim
Claim 4 covers identifying mutations or polymorphisms in genes encoding HR-pathway components. It is broader than a BRCA-only claim and can reach multigene-panel testing if the testing is used to identify the claimed HR-deficient cancer for treatment.
The claim does not require a particular mutation, sequencing technology or gene panel. Its central limitation is the relationship between the detected alteration and the HR repair pathway.
What PARP inhibitors are potentially covered?
Claim 9 specifically identifies phthalazin-1(2H)-one PARP inhibitors. Olaparib is the principal commercial example associated with this limitation. Other PARP inhibitors, including rucaparib, niraparib and talazoparib, are structurally distinct and may not satisfy claim 9. They can still be relevant to the broader claims if they are administered to a patient identified as having HR-deficient cancer.
| PARP inhibitor |
Main sponsor |
FDA status |
Relationship to US 8,071,579 |
| Olaparib |
AstraZeneca/Merck |
FDA-approved |
Primary commercial product associated with the patent |
| Rucaparib |
Clovis Oncology |
FDA-approved |
Potential relevance to broad treatment claims |
| Niraparib |
GlaxoSmithKline/Tesaro |
FDA-approved |
Potential relevance to broad treatment claims |
| Talazoparib |
Pfizer/Medivation |
FDA-approved |
Potential relevance to broad treatment claims |
| Pamiparib |
BeiGene |
Not broadly approved in the United States |
Depends on U.S. commercialization and claim scope |
FDA approval of a PARP inhibitor does not itself establish freedom to operate. Regulatory approval and patent infringement are separate inquiries.
What is the patent expiration date?
The patent’s earliest priority date is May 8, 2001, and the U.S. filing and prosecution history place the ordinary 20-year patent term in the 2022 period, subject to patent-term adjustment, patent-term extension and any terminal-disclaimer effects recorded by the USPTO.
The key date for commercial analysis is not the priority date alone. For an FDA-approved drug, a patent-term extension under 35 U.S.C. § 156 may change the enforceable expiration date. The relevant FDA regulatory review period and USPTO patent-term records must be used to determine whether the patent received an extension. The ordinary term and any regulatory extension should be treated separately in an Orange Book or launch analysis.
| Event |
Date or period |
| Earliest stated priority |
May 8, 2001 |
| U.S. patent issuance |
December 6, 2011 |
| Ordinary 20-year term analysis |
Based on the 2002 U.S./international filing history |
| Regulatory-extension issue |
Requires review of USPTO and FDA records |
| Patent type |
Method-of-treatment patent |
| Composition claim |
No |
| Formulation claim |
No |
What is the Orange Book status of US 8,071,579?
A patent covering a method of using an approved drug may be listed in the FDA Orange Book if it meets FDA listing requirements and is submitted by the NDA holder. A listing does not convert the patent into a composition patent. It gives the NDA holder a basis to assert a listed method-of-use patent against an abbreviated new drug application that includes the corresponding patented use.
For olaparib, Orange Book analysis should distinguish:
- The NDA for Lynparza;
- Listed use patents;
- Drug substance or product-by-process patents;
- Formulation patents;
- Patent expiration dates;
- FDA use codes; and
- Any pediatric-exclusivity adjustment.
A generic applicant that seeks approval for a use protected by a listed method patent may file a Paragraph IV certification. A generic applicant that omits the patented use may pursue a section viii statement, subject to FDA’s determination of whether the label can be carved out without retaining the patented indication.
What formulation patents protect olaparib?
US 8,071,579 does not claim an olaparib formulation. It claims the clinical use of PARP inhibition in HR-deficient cancer.
Separate patent families may cover:
- Olaparib free-base and salt forms;
- Crystal forms;
- Solid oral dosage forms;
- Particle-size specifications;
- Excipients and dissolution profiles;
- Manufacturing processes; and
- Specific dosing regimens.
These patents can create later-expiring barriers after the core treatment patent expires. A generic applicant therefore must conduct a separate Orange Book and non-Orange Book review of olaparib composition, formulation and process patents.
Which companies are challenging the PARP inhibitor patent estate?
Generic manufacturers seeking olaparib approval are the principal potential challengers. Paragraph IV litigation risk depends on the specific ANDA, the patents listed against the relevant NDA, the proposed label and the asserted patent claims.
The most important litigation issues are likely to include:
- Whether the generic label induces use in HR-deficient or BRCA-mutated cancer.
- Whether the proposed label carves out patented uses.
- Whether claim 1 is anticipated or rendered obvious by earlier BRCA and PARP-inhibitor publications.
- Whether the claims adequately describe and enable the full range of HR deficiencies.
- Whether the patent received valid patent-term extension.
- Whether later patents independently block launch.
A Paragraph IV certification can trigger a 30-month stay of FDA approval under the Hatch-Waxman framework if the NDA holder files a timely infringement action. A settlement may provide a licensed entry date, but a settlement date cannot be inferred from the patent claims alone.
How strong is the patent estate?
The patent has strong conceptual breadth but uneven litigation strength across its claim set.
| Risk category |
Assessment |
| Core inventive concept |
Strong: HR deficiency plus PARP inhibition |
| BRCA-specific treatment |
Stronger factual support and clinical validation |
| All HR-pathway defects |
Broader but more exposed to enablement and written-description challenges |
| Heterozygous BRCA claims |
More vulnerable because heterozygosity does not always produce functional deficiency |
| Rad51-foci assay |
Narrower and easier to design around |
| Genomic mutation claim |
Potentially broad, but requires linkage between mutation and HR deficiency |
| Olaparib-specific claim |
Commercially important where phthalazinone structure is met |
| Formulation protection |
Not provided by this patent |
| Manufacturing protection |
Not provided by this patent |
What generic launch scenarios exist?
Three launch scenarios are commercially relevant:
- Patent expiry launch. The generic launches after all enforceable patents and exclusivities expire.
- Paragraph IV launch. The generic launches after litigation, settlement or a successful invalidity or noninfringement position.
- Carve-out launch. The generic omits patented HR-deficient or BRCA-mutated indications and markets only unprotected uses.
The third scenario is difficult where the approved product’s principal commercial value is concentrated in the patented biomarker-selected population. FDA labeling, physician prescribing patterns and inducement evidence would determine practical risk.
How does US 8,071,579 compare with competing PARP patent estates?
AstraZeneca’s olaparib estate is centered on olaparib chemistry, formulation, manufacturing and treatment use. Pfizer’s talazoparib estate, GSK’s niraparib estate and Clovis’s rucaparib estate rely on different composition and clinical-use patent portfolios.
US 8,071,579 is distinctive because it protects the biological treatment principle rather than merely a molecule. Its value is highest where:
- HR-deficiency testing is integrated into prescribing;
- BRCA-mutated indications represent a material portion of revenue;
- The product is a phthalazinone PARP inhibitor; and
- Later formulation or composition patents do not independently control market entry.
Key Takeaways
- US 8,071,579 is a method-of-treatment patent for using PARP inhibition in HR-deficient cancer.
- Claim 1 is not limited to BRCA1, BRCA2, breast cancer or olaparib.
- Claims 2 through 4 cover functional HR testing, Rad51-foci assays and genomic identification of HR-pathway defects.
- Claims 6 through 8 specifically address BRCA1/2-deficient tumors, including homozygous and heterozygous mutation states.
- Claim 9 is directed to phthalazin-1(2H)-one PARP inhibitors and is commercially relevant to olaparib.
- The patent does not protect olaparib’s formulation, manufacturing process or composition by itself.
- Generic exposure depends on the proposed label, Orange Book listings, Paragraph IV certifications, carve-outs and separate later-expiring patents.
- The ordinary patent term falls in the 2022 period, but the legally operative expiration date requires the USPTO record for any patent-term adjustment or FDA patent-term extension.
- The strongest commercial protection is the combination of this treatment patent with later olaparib composition, formulation and process patents.
FAQs on US Patent 8,071,579
Does US 8,071,579 cover all PARP inhibitors?
No. The broad claims can potentially reach treatment with a PARP inhibitor, but claim 9 is limited to phthalazin-1(2H)-one compounds. Other PARP inhibitors must be assessed under the broader claims and their chemical structures.
Does a BRCA mutation automatically establish infringement?
No. The claims require identification of HR deficiency or use of the mutation to identify an HR-deficient cancer. A BRCA mutation that does not produce the claimed repair deficiency may not satisfy every limitation.
Is US 8,071,579 a formulation patent?
No. It is a biomarker-directed method-of-treatment patent. Separate patents may protect olaparib formulations, crystal forms, manufacturing processes or dosing regimens.
Can a generic launch with a label that excludes BRCA-mutated cancer?
Potentially, but the carve-out must remove the patented use from the proposed labeling and must be consistent with FDA requirements. Physician use, promotional activity and inducement evidence remain relevant to litigation risk.
Does FDA approval prove that the patent is valid?
No. FDA approval addresses safety, efficacy and regulatory requirements. Patent validity, enforceability and infringement are determined under patent law and, when litigated, by the courts.
References
- U.S. Patent and Trademark Office. (2011). U.S. Patent No. 8,071,579, Use of inhibitors of poly(ADP-ribose) polymerase in the treatment of cancer.
- U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book.
- U.S. Food and Drug Administration. (2014). Lynparza (olaparib) prescribing information.
- Congress of the United States. (2023). 35 U.S.C. §§ 156, 271, and 282.
- Bryant, H. E., Schultz, N., Thomas, H. D., Parker, K. M., Flower, D., Lopez, E., Kyle, S., Meuth, M., Curtin, N. J., & Helleday, T. (2005). Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature, 434(7035), 913-917.
- Farmer, H., McCabe, N., Lord, C. J., Tutt, A. N. J., Johnson, D. A., Richardson, T. B., Santarosa, M., Dillon, K. J., Hickson, I., Knights, C., et al. (2005). Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature, 434(7035), 917-921.
