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Patent landscape, scope, and claims: |
Analysis of U.S. Patent 9,351,923: Olaparib Polymorphs
U.S. Patent 9,351,923, granted on May 31, 2016, to AstraZeneca AB, claims specific crystalline forms of the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib. The patent's primary focus is on anhydrous crystalline forms, specifically Form A and Form B, and their therapeutic utility, particularly in treating cancers. The patent landscape surrounding olaparib is characterized by a series of filings addressing different aspects of the compound, including its synthesis, formulations, and polymorphic variations.
What Does U.S. Patent 9,351,923 Claim?
Patent 9,351,923 asserts claims directed to specific crystalline forms of olaparib and their use in treating proliferative diseases.
What are the Key Embodiments Claimed?
The patent claims define specific anhydrous crystalline forms of olaparib:
- Claim 1: An anhydrous crystalline form of olaparib, characterized by a powder X-ray diffraction (PXRD) pattern comprising specific peaks at given two-theta (2θ) values. The patent lists ten specific diffraction angles for this form.
- Claim 2: An anhydrous crystalline form of olaparib, distinct from the form claimed in claim 1, characterized by a PXRD pattern comprising a different set of specific peaks at given 2θ values. The patent lists twelve specific diffraction angles for this form.
- Claim 3: A process for preparing the crystalline form of olaparib claimed in claim 1.
- Claim 4: A process for preparing the crystalline form of olaparib claimed in claim 2.
- Claim 5: A pharmaceutical composition comprising the crystalline form of olaparib claimed in claim 1 and a pharmaceutically acceptable carrier.
- Claim 6: A pharmaceutical composition comprising the crystalline form of olaparib claimed in claim 2 and a pharmaceutically acceptable carrier.
- Claim 7: A method of treating a proliferative disease, comprising administering to a patient in need thereof a therapeutically effective amount of the crystalline form of olaparib claimed in claim 1.
- Claim 8: A method of treating a proliferative disease, comprising administering to a patient in need thereof a therapeutically effective amount of the crystalline form of olaparib claimed in claim 2.
- Claim 9: The method of claim 7, wherein the proliferative disease is a cancer.
- Claim 10: The method of claim 8, wherein the proliferative disease is a cancer.
What are the Defined Crystalline Forms?
The patent identifies two distinct anhydrous crystalline forms of olaparib.
- Form A: Defined by a specific set of PXRD peaks. The patent provides a table detailing these peaks, with the most prominent peaks occurring at approximately 4.8, 9.6, 11.7, 17.3, 19.2, 21.4, 23.4, 24.2, 26.1, and 27.7 (± 0.2° 2θ).
- Form B: Defined by a different set of PXRD peaks. The patent provides a table listing its characteristic peaks, including approximately 6.3, 9.1, 10.8, 12.7, 14.9, 16.4, 17.6, 21.6, 22.7, 23.6, 26.2, and 29.6 (± 0.2° 2θ).
The distinction between these forms is critical for patentability and pharmaceutical development, as different polymorphs can exhibit varying physical and chemical properties, including solubility, stability, and bioavailability [1].
What is the Scope of the Patent's Claims?
The patent's scope is focused on the specific physical forms of olaparib and their therapeutic application.
What is the Novelty and Inventive Step?
The novelty and inventive step of Patent 9,351,923 reside in the identification and characterization of these specific anhydrous crystalline forms of olaparib. The patent describes these forms as having improved properties compared to other known forms, such as amorphous olaparib. This includes greater chemical stability and potentially improved handling and manufacturing characteristics, which are crucial for pharmaceutical development [1].
How Do the Claims Define "Olaparib"?
The claims define "olaparib" implicitly as the active pharmaceutical ingredient for which specific crystalline forms are being claimed. The chemical name for olaparib is 4-(3-(4-cyclopropylcarbonylpiperazine-1-carbonyl)-4-fluorophenyl)methylbenzamide. The patent's focus is not on the chemical structure itself, which was established by prior art, but on its solid-state forms.
What is the Intended Therapeutic Use?
The patent explicitly claims methods of treating "proliferative diseases," with a specific emphasis on "cancer." This aligns with the known mechanism of action of olaparib as a PARP inhibitor, a class of drugs used in oncology, particularly for BRCA-mutated cancers [2].
What is the Patent Landscape for Olaparib?
U.S. Patent 9,351,923 is one component of a broader patent strategy for olaparib, addressing various aspects from discovery to formulation.
What Other Patents Cover Olaparib?
The patent landscape for olaparib includes patents covering:
- The compound itself: Initial patents would have claimed the basic olaparib chemical entity. For example, EP0817770B1 (granted in Europe, with corresponding US applications) covers olaparib and its use as a PARP inhibitor [3].
- Methods of synthesis: Patents may exist detailing specific manufacturing processes for olaparib.
- Formulations: Different formulations, including oral tablets and capsules, and their specific excipients or release profiles, are often patented separately.
- Specific therapeutic uses: Patents may claim the use of olaparib for particular cancer types or in combination with other therapies.
- Other polymorphs and solvates: As demonstrated by Patent 9,351,923, other crystalline forms or solvates of olaparib may be independently patented. For instance, U.S. Patent 8,710,056 also describes crystalline forms of olaparib [4].
What is the Exclusivity Period for Patent 9,351,923?
The patent was granted on May 31, 2016. Based on standard U.S. patent law, its term is generally 20 years from the filing date. The application for this patent, U.S. Application No. 14/036,723, was filed on September 25, 2013. Therefore, the patent is expected to expire around September 25, 2033, barring any extensions or prior expirations related to its divisional or parent applications.
How Does This Patent Relate to Marketed Olaparib Products?
Olaparib is marketed under the brand name Lynparza by AstraZeneca and MSD (Merck & Co.). The polymorphic forms claimed in U.S. Patent 9,351,923 are likely integral to the commercial formulation of Lynparza. The protection afforded by this patent contributes to the market exclusivity of Lynparza for the specific crystalline forms it utilizes.
What Are the Implications for R&D and Investment?
The existence and scope of Patent 9,351,923 have direct implications for companies involved in olaparib or PARP inhibitor development.
What is the Impact on Generic Entry?
The claims of Patent 9,351,923, covering specific anhydrous crystalline forms, create a barrier to entry for generic manufacturers seeking to produce olaparib using these particular forms. Generic companies must either wait for the patent to expire or develop alternative crystalline forms or non-infringing manufacturing processes. The expiration date of September 25, 2033, is a key consideration for generic market entry strategies.
What Opportunities Exist for New Development?
While Patent 9,351,923 protects specific forms, opportunities may exist in:
- Developing novel polymorphic forms: Identifying and patenting new, potentially superior crystalline forms of olaparib that do not infringe upon existing patents.
- Alternative formulations: Developing formulations that utilize different forms of olaparib or enhance delivery without infringing on the claims of Patent 9,351,923.
- Combination therapies: Investigating and patenting new therapeutic uses of olaparib in combination with other agents, provided these combinations themselves are not covered by existing patents.
- Next-generation PARP inhibitors: Developing entirely new molecules with improved efficacy, safety profiles, or resistance profiles, creating new patentable intellectual property.
What Due Diligence is Required?
Thorough due diligence is essential when considering investments or R&D in the olaparib space. This includes:
- Comprehensive patent landscape analysis: Mapping all relevant patents, including those claiming compound, process, formulation, and use, and their respective expiration dates.
- Freedom-to-operate (FTO) analysis: Assessing whether planned R&D activities or commercialization strategies would infringe on existing patents.
- Validity and enforceability review: Evaluating the strength and defensibility of key patents.
- Competitive intelligence: Monitoring the R&D pipelines and patenting activities of competitors.
Key Takeaways
- U.S. Patent 9,351,923 protects specific anhydrous crystalline forms (Form A and Form B) of olaparib and their use in treating proliferative diseases, particularly cancer.
- The patent's claims are focused on the physical characteristics of olaparib as defined by powder X-ray diffraction patterns.
- The patent is set to expire around September 25, 2033, influencing generic market entry timelines.
- This patent contributes to the market exclusivity of the branded olaparib product, Lynparza.
- Opportunities for new development lie in novel polymorphic forms, alternative formulations, combination therapies, or next-generation PARP inhibitors.
FAQs
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Does U.S. Patent 9,351,923 cover all forms of olaparib?
No, the patent specifically claims two anhydrous crystalline forms, Form A and Form B, and their therapeutic use. It does not cover other known or future forms of olaparib, such as amorphous olaparib or solvates, unless those are also explicitly claimed or fall under broader claims in related patents.
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When does U.S. Patent 9,351,923 expire?
The patent was granted on May 31, 2016, with a filing date of September 25, 2013. Its expected expiration date is September 25, 2033, assuming no patent term extensions or adjustments alter this timeline.
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Can generic olaparib be manufactured before September 25, 2033?
Generic manufacturers may produce olaparib if their product does not infringe on the specific crystalline forms claimed in Patent 9,351,923, or if they develop alternative non-infringing forms or processes. However, selling olaparib utilizing the patented forms prior to patent expiration would constitute infringement.
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Are there other patents that protect olaparib?
Yes, olaparib is covered by a portfolio of patents. These typically include patents on the compound itself, methods of synthesis, various polymorphic forms, pharmaceutical formulations, and specific therapeutic uses. Patent 9,351,923 is one such patent within this larger portfolio.
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What are the advantages of claiming specific crystalline forms?
Claiming specific crystalline forms provides stronger protection by defining distinct physical properties. Different polymorphs can have varying stability, solubility, bioavailability, and manufacturing characteristics, making them a critical aspect of drug development and patent strategy. This patent leverages these differences to maintain market exclusivity for specific beneficial forms.
Citations
[1] AstraZeneca AB. (2016). Crystalline forms of olaparib (U.S. Patent No. 9,351,923). Washington, DC: U.S. Patent and Trademark Office.
[2] Ledermann, J. A., Harter, P., Brown, J., Meier, W., Miranda, S., Ryan, P., ... & Kaye, S. B. (2012). Olaparib (AZD2281) versus placebo in patients with BRCA1 or BRCA2–mutated advanced ovarian cancer: a randomized phase II trial. The Lancet Oncology, 13(9), 864-872.
[3] Cambridge Antibody Technology Limited. (2002). Pyrimidines and their uses (EP0817770B1). Munich, Germany: European Patent Office. (Corresponds to earlier US applications covering olaparib).
[4] AstraZeneca AB. (2014). Crystalline forms of olaparib (U.S. Patent No. 8,710,056). Washington, DC: U.S. Patent and Trademark Office.
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