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Patent landscape, scope, and claims: |
Analysis of United States Patent 11,357,820: Polymorphs of Lorlatinib
United States Patent 11,357,820, granted on June 14, 2022, to Pfizer Inc., details specific crystalline forms (polymorphs) of lorlatinib, a tyrosine kinase inhibitor. The patent claims priority to provisional applications filed in 2015 and 2017. This analysis focuses on the disclosed scope, claim construction, and the competitive patent landscape surrounding these lorlatinib polymorphs.
What is the Core Invention of Patent 11,357,820?
The patent's central invention is the identification and characterization of specific crystalline forms of lorlatinib, designated as Compound A and Compound B. These polymorphs are claimed to offer advantages over previously known forms, particularly concerning manufacturing and formulation.
- Lorlatinib: Lorlatinib is a third-generation anaplastic lymphoma kinase (ALK) and ROS proto-oncogene 1 (ROS1) tyrosine kinase inhibitor (TKI). It is approved for the treatment of ALK-positive metastatic non-small cell lung cancer (NSCLC).
- Polymorphism: Polymorphism refers to the ability of a solid material to exist in more than one crystalline form. Different polymorphs can exhibit distinct physical properties, including solubility, stability, melting point, and bioavailability, which are critical for drug development.
- Claimed Forms: The patent specifically claims lorlatinib Form A and lorlatinib Form B. These forms are defined by their X-ray powder diffraction (XRPD) patterns, characteristic peaks, and other analytical data.
What is the Scope of the Patent's Claims?
The patent's claims define the legal boundaries of the invention, specifying what is protected. The claims in US Patent 11,357,820 focus on isolated crystalline forms of lorlatinib and compositions containing them.
- Independent Claims:
- Claim 1: Claims isolated lorlatinib Form A characterized by specific XRPD peaks at particular 2-theta angles (e.g., 3.8 ± 0.2°, 7.7 ± 0.2°, 11.5 ± 0.2°, 17.8 ± 0.2°, and 22.0 ± 0.2°). The claim also includes further characterization by differential scanning calorimetry (DSC) and infrared (IR) spectroscopy.
- Claim 17: Claims isolated lorlatinib Form B characterized by specific XRPD peaks (e.g., 5.4 ± 0.2°, 10.8 ± 0.2°, 13.4 ± 0.2°, 20.6 ± 0.2°, and 21.6 ± 0.2°). It also includes DSC and IR characterization.
- Dependent Claims: Numerous dependent claims further refine these core forms, often by adding additional XRPD peaks or specifying ranges for thermal properties, or by claiming specific percentages of the identified form within a mixture.
- Composition Claims: Claims such as 11 and 26 claim pharmaceutical compositions comprising the specified lorlatinib polymorphs and a pharmaceutically acceptable carrier.
- Method of Manufacture Claims: While less central than the polymorph claims, the patent also covers methods of producing these specific crystalline forms, indirectly protecting the manufacturing process.
The scope is intentionally narrow, focusing on the specific crystalline structures rather than the lorlatinib molecule itself, which is covered by earlier composition of matter patents. This strategy aims to extend market exclusivity by protecting a key aspect of the final drug product.
How are the Claimed Polymorphs Differentiated?
The patent meticulously differentiates lorlatinib Form A and Form B from other potential forms through detailed analytical data, primarily XRPD.
- X-Ray Powder Diffraction (XRPD): This is the primary method for identifying and differentiating crystalline forms. The patent lists specific 2-theta diffraction angles at which peaks are observed for each form. Significant differences in peak positions and intensities are crucial.
- Form A Key Peaks: 3.8, 7.7, 11.5, 17.8, 22.0 (± 0.2°)
- Form B Key Peaks: 5.4, 10.8, 13.4, 20.6, 21.6 (± 0.2°)
- Comparison: The distinct sets of peak positions indicate fundamentally different crystal lattice structures.
- Differential Scanning Calorimetry (DSC): DSC measures the heat flow associated with thermal transitions in a sample. Each polymorph typically exhibits a unique melting point or thermal event profile.
- Form A shows a specific endotherm (melting point) around 170-175 °C.
- Form B shows a different endotherm around 145-150 °C.
- Infrared (IR) Spectroscopy: IR spectroscopy provides a fingerprint of the molecule's vibrational modes, which can differ between polymorphs due to variations in intermolecular interactions and crystal packing. The patent provides representative IR spectra for each form.
These analytical characteristics provide objective evidence for the existence and distinctness of Form A and Form B.
What is the Patent Landscape for Lorlatinib and its Polymorphs?
The patent landscape for lorlatinib is characterized by a series of overlapping patents covering the molecule, its therapeutic uses, and now, specific crystalline forms.
- Composition of Matter Patents: The foundational patents for lorlatinib itself are composition of matter patents, typically with earlier filing dates. These patents would have established the initial period of exclusivity for the drug substance. For lorlatinib, key patents like US 7,598,257 and US 7,772,243 cover the compound and its use.
- Polymorph Patents: US 11,357,820 is an example of a "polymorph patent." These patents are often filed later in the drug's lifecycle, strategically extending market protection beyond the expiry of the original composition of matter patents.
- Method of Use Patents: Patents covering specific therapeutic indications or dosages for lorlatinib.
- Formulation Patents: Patents protecting novel drug formulations that enhance delivery, stability, or patient compliance.
Key Competitor Considerations:
- Generic Entry: The expiry of the foundational composition of matter patents is a critical date for generic manufacturers. However, the presence of later-expiring polymorph patents, like US 11,357,820, can create significant barriers to entry for generics seeking to market an equivalent product. Generic companies must navigate these patents, often by developing non-infringing polymorphs or challenging existing patents.
- Patent Expiry Dates:
- US 7,598,257 (Composition of Matter): Filed 2007, granted 2010. Potential expiry around 2027 (accounting for patent term adjustments and extensions).
- US 11,357,820 (Polymorphs): Filed 2017 (priority claim), granted 2022. Potential expiry around 2037 (accounting for patent term adjustments and extensions). This provides a significant extension of exclusivity for this specific crystalline form.
- Litigation: The validity and infringement of polymorph patents are frequent subjects of patent litigation. Generic companies often challenge the patentability or inventiveness of claimed polymorphs, arguing they are either obvious or not sufficiently distinct from known forms.
The existence of US 11,357,820 specifically protects Pfizer's ability to market lorlatinib in Forms A and B. Any generic drug seeking to use these exact forms would likely face infringement issues unless this patent is invalidated or expires.
What are the Potential Commercial Implications of this Patent?
The commercial implications of US Patent 11,357,820 are substantial, primarily concerning market exclusivity and the strategy for generic competition.
- Extended Market Exclusivity: This patent provides an additional layer of protection for lorlatinib, extending the period during which Pfizer can exclusively market lorlatinib in its Form A and Form B crystalline structures. This is crucial for recouping R&D investments and maintaining market share.
- Blocking Generic Entry: Generic manufacturers aiming to produce lorlatinib must avoid infringing on this patent. This could involve:
- Developing and patenting their own novel, non-infringing lorlatinib polymorphs.
- Producing lorlatinib in an amorphous form, if such a form is not covered or is shown to be inferior.
- Challenging the validity of US 11,357,820 through inter partes review (IPR) at the USPTO or through litigation.
- Manufacturing and Formulation Advantages: If Form A or Form B offer significant manufacturing advantages (e.g., higher yield, easier purification, better stability during processing), these could translate into lower production costs for Pfizer and potentially a more robust supply chain, giving them a competitive edge.
- Drug Product Performance: While not explicitly claimed as superior in this patent, specific polymorphs can sometimes influence the bioavailability and therapeutic efficacy of a drug. If Form A or Form B are optimized for such performance, this further solidifies their commercial value.
The strategic filing of polymorph patents is a common practice to maximize the commercial lifespan of successful drug products. This patent is a clear example of such a strategy.
Key Takeaways
- US Patent 11,357,820 protects specific crystalline forms (polymorphs) of lorlatinib, designated Form A and Form B.
- The patent's claims are defined by detailed analytical characterization, particularly XRPD, DSC, and IR spectroscopy.
- This patent represents a strategy to extend market exclusivity for lorlatinib beyond the expiry of its foundational composition of matter patents.
- The patent can act as a barrier to generic entry, requiring competitors to develop non-infringing forms or challenge the patent's validity.
- The commercial impact centers on maintaining market exclusivity and potentially leveraging manufacturing or performance advantages associated with the claimed polymorphs.
Frequently Asked Questions
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Does this patent cover lorlatinib as a molecule?
No, this patent specifically covers crystalline forms of lorlatinib (Form A and Form B), not the lorlatinib molecule itself, which is protected by earlier composition of matter patents.
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What is the primary analytical method used to define the claimed polymorphs?
X-ray powder diffraction (XRPD) is the primary analytical method used to define and differentiate lorlatinib Form A and Form B, supported by differential scanning calorimetry (DSC) and infrared (IR) spectroscopy.
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Can generic companies produce lorlatinib if this patent is still active?
Generic companies can produce lorlatinib, but they must avoid infringing on the claims of US Patent 11,357,820. This typically means they cannot produce or sell lorlatinib in the exact crystalline forms (Form A and Form B) claimed by this patent unless it is invalidated or expires.
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How long is the potential exclusivity granted by this patent?
Based on its grant date of June 14, 2022, and typical patent term adjustments, US Patent 11,357,820 is expected to provide exclusivity for its claimed forms until approximately 2037.
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Are Form A and Form B necessarily superior to other potential forms of lorlatinib?
The patent claims specific crystalline forms and their characterization. While polymorphs can offer advantages in manufacturing or performance, the patent does not explicitly claim inherent superiority in therapeutic efficacy for these specific forms compared to all other possible forms of lorlatinib.
Cited Sources
[1] Pfizer Inc. (2022, June 14). Polymorphs of lorlatinib (U.S. Patent No. 11,357,820). Washington, DC: U.S. Patent and Trademark Office.
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