US Patent 8,475,842: Olaparib Solid-Dispersion Claims, Patent Scope and Generic-Entry Risk
US Patent 8,475,842 protects immediate-release olaparib compositions in which the active pharmaceutical ingredient is dispersed in copovidone at defined drug-loading and drug-to-polymer ratios. The strongest commercial embodiment is a melt-extruded, predominantly amorphous solid dispersion containing 25% olaparib, a 1:2.3 olaparib-to-copovidone ratio, colloidal silicon dioxide, mannitol, and sodium stearyl fumarate.
The patent is formulation-specific. It does not broadly protect olaparib as a molecule, PARP inhibition generally, or every olaparib tablet. A competing product must satisfy every limitation of at least one asserted claim to infringe.
What drug and formulation does US 8,475,842 cover?
Compound 1 is olaparib, also known as AZD2281 and KU-0059436. Olaparib is a PARP1 and PARP2 inhibitor marketed by AstraZeneca and Merck & Co. as Lynparza.
The claimed dosage form has five central technical elements:
- Immediate release.
- A solid dispersion.
- Olaparib or an olaparib salt as the active phase.
- Copovidone as the carrier phase.
- A specified olaparib concentration and olaparib-to-copovidone weight ratio.
The patent therefore targets dissolution and bioavailability problems associated with the poorly water-soluble active ingredient. Copovidone stabilizes the dispersed amorphous olaparib phase and supports rapid release.
| Claim element |
Required limitation |
| Active ingredient |
Olaparib or a salt of olaparib |
| Dosage form |
Immediate-release pharmaceutical composition |
| Physical form |
Solid dispersion |
| Polymer carrier |
Copovidone |
| Drug concentration |
20% to 30% by weight in claims 1 and 6 |
| Drug amount |
25 to 400 mg in claim 1; 10 to 1,000 mg in claim 6 |
| Drug-to-polymer ratio |
1:2 to 1:4 in claims 1 and 6 |
| Amorphous content |
Expressly required only by claims 2 and 3 |
| Manufacturing process |
Solvent evaporation or melt extrusion in claim 4; melt extrusion in claim 5 |
| Narrow commercial formulation |
25% olaparib and a 1:2.3 olaparib-to-copovidone ratio in claim 7 |
The claims use “total concentration” and “total amount.” Those terms capture the amount of olaparib in the complete composition rather than only the active phase.
What are the independent claims in US Patent 8,475,842?
Claims 1, 6, and 7 are independent composition claims. They overlap, but they are not identical.
Claim 1: 25 mg to 400 mg formulation range
Claim 1 requires:
- 20% to 30% olaparib by weight;
- 25 mg to 400 mg total olaparib;
- a 1:2 to 1:4 olaparib-to-copovidone ratio; and
- an immediate-release solid dispersion.
Claim 1 is narrower than claim 6 in dose amount but includes the same key formulation ranges.
Claim 6: broader dose range
Claim 6 extends the olaparib amount to 10 mg to 1,000 mg. It retains the 20% to 30% concentration and 1:2 to 1:4 ratio.
The practical significance is substantial. A product containing 10 mg to 1,000 mg of olaparib may fall within claim 6 even if it is outside claim 1’s 25 mg to 400 mg amount range.
Claim 7: narrow composition centered on 25% olaparib
Claim 7 requires:
- 25% olaparib by weight;
- a 1:2.3 olaparib-to-copovidone ratio;
- an immediate-release solid dispersion; and
- copovidone as the carrier phase.
Claim 7 does not recite a separate dose-amount range. It is a highly specific composition claim directed to a formulation point within the broader ranges of claims 1 and 6.
How do the dependent claims narrow the patent scope?
| Claim |
Added limitation |
Commercial significance |
| 2 |
Olaparib is amorphous |
Excludes formulations in which the claimed olaparib is not amorphous |
| 3 |
At least 90% of olaparib is amorphous |
Creates a measurable solid-state limitation |
| 4 |
Composition made by solvent evaporation or melt extrusion |
Narrows the product claim through a manufacturing limitation |
| 5 |
Composition made by melt extrusion |
More specific process limitation |
| 8 |
Glidant, soluble filler, and lubricant |
Captures conventional tablet-excipient combinations |
| 9 |
Colloidal silicon dioxide, mannitol, and sodium stearyl fumarate |
Identifies a specific excipient set |
| 10 |
1.8% colloidal silicon dioxide, 14.7% mannitol, and 1% sodium stearyl fumarate |
Closest claim to a defined commercial tablet composition |
Claims 9 and 10 are particularly relevant to finished-tablet comparisons. A generic manufacturer could avoid those claims by changing one or more excipients or their concentrations, while still potentially infringing claims 1, 6, or 7.
What formulation is most directly exposed to US 8,475,842?
The highest-risk formulation is a tablet or other immediate-release dosage form with the following profile:
| Parameter |
Claimed profile |
| Active |
Olaparib |
| Release |
Immediate |
| Solid state |
Amorphous or predominantly amorphous |
| Carrier |
Copovidone |
| Drug loading |
25% |
| Drug-to-copovidone ratio |
1:2.3 |
| Process |
Melt extrusion |
| Other excipients |
Colloidal silicon dioxide, mannitol, sodium stearyl fumarate |
| Excipient levels |
1.8%, 14.7%, and 1%, respectively |
A product matching this profile would potentially read on claim 7 and, depending on dose and processing facts, claims 1, 2, 3, 5, 6, 9, and 10.
Does the patent require an amorphous olaparib formulation?
No for the broad independent claims, but yes for certain dependent claims.
Claims 1, 6, and 7 do not expressly require that olaparib be amorphous. They require a solid dispersion. Claims 2 and 3 add amorphous limitations, with claim 3 requiring at least 90% amorphous olaparib.
This distinction matters in infringement analysis:
- A crystalline or partially crystalline solid dispersion may still be tested against claims 1, 6, and 7.
- It would not satisfy claim 2 if olaparib is not amorphous.
- It would not satisfy claim 3 unless at least 90% of the olaparib is amorphous.
- The measurement method for “at least 90%” would likely become a central expert and claim-construction issue.
The patent record should be read together with solid-state characterization data, including powder X-ray diffraction, differential scanning calorimetry, microscopy, and residual-solvent analysis.
What manufacturing processes are protected?
Claims 4 and 5 specifically identify solvent evaporation and melt extrusion.
Melt extrusion is the more commercially important process because it can produce a continuous polymer matrix with controlled drug dispersion. It also creates an infringement risk where a generic manufacturer uses the same process even if the finished tablet is not identical in excipient composition.
The process claims do not mean that every melt-extruded olaparib product infringes. The product must still satisfy the underlying composition limitations, including copovidone, concentration, ratio, and immediate-release characteristics.
A process that uses spray drying, fluid-bed coating, mechanical blending, or another manufacturing route may avoid claims 4 and 5. It could still fall within claims 1, 6, or 7 if the resulting product has the required composition and physical characteristics.
When does US Patent 8,475,842 expire?
US Patent 8,475,842 was issued on July 2, 2013. Its published priority chain traces to a January 2009 British priority filing, with an international filing in 2010. The ordinary US patent term is therefore expected to run into 2030, subject to the official term calculation, patent-term adjustment, terminal disclaimers, and any post-grant legal events. [1]
| Event |
Date or period |
| Earliest reported priority |
January 2009 |
| International filing period |
2010 |
| US patent grant |
July 2, 2013 |
| Expected nominal US term |
Approximately January 2030 |
| Patent type |
Utility formulation patent |
| Patent status relevant to generic planning |
Unexpired during the expected generic-entry window, absent an earlier legal termination |
The patent’s expiration date should not be confused with olaparib’s basic compound-patent expiration. Different patents in the Lynparza estate can expire at different times and protect different aspects of the product.
What other patents protect olaparib and Lynparza?
The commercial olaparib estate includes several patent categories:
| Patent category |
Subject matter |
Generic-entry effect |
| Compound patents |
Olaparib chemical structure and related phthalazinone derivatives |
Can block the active ingredient itself |
| Solid-state and formulation patents |
Amorphous dispersion, polymers, dosage forms, and excipients |
Can block particular tablets or capsules |
| Method-of-use patents |
Ovarian, breast, pancreatic, prostate, and other cancer indications |
Can support use-code or labeling restrictions |
| Combination patents |
Olaparib with other anticancer agents |
Relevant to combination indications |
| Manufacturing patents |
API synthesis, purification, polymorph control, and formulation processing |
May create supply-chain or process risk |
| Regulatory exclusivity |
New chemical entity, orphan, pediatric, or indication exclusivity |
Can delay approval independently of patent expiry |
The original olaparib compound protection is generally associated with AstraZeneca’s earlier phthalazinone patent family, including US Patent 7,915,307. Later Lynparza patents cover formulations, combinations, and additional clinical uses. [2]
US 8,475,842 should therefore be analyzed as one layer of a multi-patent estate rather than as the sole barrier to generic olaparib.
What is the Orange Book status of US 8,475,842?
The FDA Orange Book lists patents submitted by an NDA holder for an approved drug and its approved uses or formulations. The presence or absence of a patent listing directly affects the type of certification required from an ANDA applicant.
Lynparza is approved in tablet and capsule presentations. The principal publicly identified Orange Book entries for olaparib have historically included compound and later-use patents. US 8,475,842 should not automatically be treated as an Orange Book-listed patent merely because it covers an olaparib formulation. Listing depends on whether AstraZeneca submitted the patent for the approved drug and whether the FDA accepted the listing under its patent-listing standards. [3]
The regulatory distinction is important:
- A listed patent can trigger a Paragraph IV notice and a potential 30-month stay.
- An unlisted formulation patent may still support a separate infringement action.
- A non-listed patent generally does not create the same ANDA certification pathway.
- A generic applicant must still address listed patents and applicable method-of-use patents even if it designs around US 8,475,842.
What Paragraph IV challenges and litigation risks exist?
A Paragraph IV challenge is most likely to target the earliest blocking compound patent or a listed method-of-use patent. A formulation patent becomes more important when:
- The generic applicant uses the same or similar solid-dispersion technology.
- The formulation patent is listed for the approved dosage form.
- The compound patent has expired or is vulnerable.
- The generic filing seeks approval before the formulation patent expires.
For US 8,475,842, likely defenses include:
- The product is not an immediate-release solid dispersion.
- The carrier is not copovidone.
- The drug-to-polymer ratio is outside 1:2 to 1:4.
- Olaparib concentration is outside 20% to 30%.
- The dosage form uses a different solid-state structure.
- The product contains less than 10 mg or more than 1,000 mg, where relevant to claim 6.
- The manufacturing process is not solvent evaporation or melt extrusion, for claims 4 and 5.
- The patent claims are invalid for lack of novelty, obviousness, indefiniteness, or insufficient written description.
The strongest invalidity argument would likely focus on obviousness if prior art disclosed olaparib, copovidone, amorphous solid dispersions, and comparable loading ratios. The strongest infringement argument would focus on analytical matching of the polymer ratio, amorphous fraction, drug loading, and release profile.
No biosimilar pathway applies. Olaparib is a small molecule, so the relevant competitors would file ANDAs, not abbreviated biologics applications.
What generic launch scenarios exist?
Early launch after compound-patent expiry
A generic may seek approval after expiry of the relevant compound patent while challenging or avoiding formulation patents. This is the most commercially important pathway if US 8,475,842 is not listed or if the generic uses a materially different formulation.
At-risk launch after Paragraph IV litigation
A generic may launch before final resolution of listed patents after providing a Paragraph IV notice. This exposes the applicant to damages and injunctive risk if the patent holder prevails.
Formulation design-around
A generic could change:
- The carrier polymer;
- The drug-to-polymer ratio;
- Olaparib concentration;
- The manufacturing process;
- The crystalline or amorphous state;
- The immediate-release profile;
- The excipient system.
A design-around that replaces copovidone is likely the cleanest technical strategy, but it may create new dissolution, stability, or bioequivalence challenges.
Authorized generic or license
AstraZeneca or a licensee could supply an authorized generic or settle with an ANDA filer. Settlement terms may include a delayed entry date, a license, or restrictions tied to specific dosage forms and indications. Commercial terms are not established by the patent claims alone.
How strong is the patent estate?
US 8,475,842 has meaningful but limited strength.
| Strength factor |
Assessment |
| Claim breadth |
Moderate; independent claims cover defined formulation ranges, not all olaparib products |
| Technical specificity |
High |
| Design-around difficulty |
Moderate |
| Dependence on analytical testing |
High |
| Dependence on Orange Book listing |
Potentially high for ANDA timing |
| Compound-level blocking power |
None by itself |
| Manufacturing relevance |
High for melt-extrusion products |
| Litigation value |
Highest against a matching amorphous copovidone dispersion |
| Biosimilar relevance |
None |
The patent is strongest against a generic that copies the 25% olaparib, 1:2.3 copovidone formulation and uses melt extrusion. It is weaker against a product using a different carrier, a different solid-state approach, or a formulation outside the claimed concentration and ratio windows.
What commercial revenue is exposed?
Lynparza is a multibillion-dollar oncology product. AstraZeneca reported approximately $2.8 billion in 2023 Lynparza revenue. [4] The revenue exposure attributable solely to US 8,475,842 cannot be separated from the broader compound, method-of-use, regulatory, and commercial estate.
The economic risk rises as compound and use patents expire because formulation patents can become the remaining basis for delaying or litigating generic entry. A formulation patent with narrow claims may not preserve the full branded market, but it can delay a closely copied product and increase the cost of a generic launch.
Key Takeaways
- US 8,475,842 covers immediate-release olaparib solid dispersions using copovidone.
- Claims 1 and 6 require 20% to 30% olaparib and a 1:2 to 1:4 olaparib-to-copovidone ratio.
- Claim 6 has the broader dose range, from 10 mg to 1,000 mg.
- Claim 7 targets a particularly important formulation: 25% olaparib and a 1:2.3 ratio.
- Claims 2 and 3 add amorphous-form limitations, with claim 3 requiring at least 90% amorphous olaparib.
- Claims 4 and 5 focus on solvent evaporation and melt extrusion.
- Claims 9 and 10 cover specific excipients and concentrations.
- The patent is expected to remain relevant until approximately 2030, subject to the official US term calculation.
- It does not independently protect olaparib as a molecule or block every generic olaparib product.
- The principal generic strategies are a different carrier polymer, an alternative solid-state form, a different drug-to-polymer ratio, or a non-covered manufacturing route.
- No biosimilar pathway applies because olaparib is a small molecule.
FAQs
Is US 8,475,842 a compound patent for olaparib?
No. It is a formulation patent. The claims require an immediate-release solid dispersion containing olaparib and copovidone at specified concentrations and ratios.
Can a generic olaparib tablet avoid US 8,475,842?
Yes, if it does not satisfy at least one limitation of every asserted claim. Replacing copovidone, changing the drug-to-polymer ratio, or using a different dosage-form technology may create a design-around.
Does a crystalline olaparib formulation infringe the patent?
Possibly. Claims 1, 6, and 7 do not expressly require amorphous olaparib. Claims 2 and 3 do. The answer depends on the solid-dispersion structure and other claim limitations.
Does the patent cover olaparib capsules?
Potentially. The claims are directed to a composition rather than a particular tablet shape. A capsule could fall within the claims if it contains the required immediate-release solid dispersion and satisfies the concentration and ratio limitations.
Is US 8,475,842 enough to delay all generic Lynparza launches?
No. Generic entry depends on the full patent and regulatory estate, including compound patents, listed method-of-use patents, formulation patents, Paragraph IV litigation, and FDA exclusivity. US 8,475,842 is one formulation-specific barrier.
References
- United States Patent and Trademark Office. (2013). US Patent No. 8,475,842, pharmaceutical composition claims covering olaparib solid dispersions.
- United States Patent and Trademark Office. (2012). US Patent No. 7,915,307, phthalazinone derivatives.
- U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book.
- AstraZeneca PLC. (2024). Annual report and Form 20-F for the year ended December 31, 2023.
