Analysis of United States Drug Patent 9,918,973: Scope, Claims, and Landscape

Patent US 9,918,973, titled "SELECTIVE CYCLIN-DEPENDENT KINASE INHIBITORS," was granted on May 15, 2018, to Pfizer Inc. The patent describes small molecule inhibitors targeting cyclin-dependent kinases (CDKs), specifically CDK4 and CDK6. These kinases play a critical role in cell cycle progression, and their dysregulation is implicated in various cancers. The patent's claims are directed towards specific chemical compounds, pharmaceutical compositions containing these compounds, and methods of treating CDK-related disorders using them. The patent landscape reveals a competitive environment for CDK inhibitors, with multiple companies actively pursuing this therapeutic avenue.

What is the Core Technology Protected by Patent US 9,918,973?

The patent protects a class of chemical compounds defined by Markush structures, which are generic representations of chemical molecules. These compounds are designed to selectively inhibit the activity of CDK4 and CDK6. The patent provides specific examples of such compounds and details their synthesis and in vitro and in vivo biological activity.

The disclosed compounds generally share a core chemical scaffold with various substituents that confer specificity and potency against CDK4 and CDK6. The utility of these inhibitors lies in their ability to block the progression of the cell cycle at the G1/S phase transition, thereby arresting the proliferation of cancer cells that depend on CDK4/6 activity for growth.

The patent details the synthesis of these compounds using standard organic chemistry methodologies. It also includes data from cell-based assays and animal models demonstrating the efficacy of these inhibitors in reducing tumor growth.

What are the Key Claims of Patent US 9,918,973?

Patent US 9,918,973 contains multiple independent and dependent claims that define the scope of protection. The most significant claims include:

Claim 1: The Core Compound Definition

Claim 1 defines a specific genus of chemical compounds. The claim is highly structured, outlining a core chemical structure with variable substituents (R1, R2, R3, R4, R5, R6, and R7) at defined positions. These substituents are described by a range of chemical groups, functional moieties, and specific heterocycles. For example:

R1 may be hydrogen, alkyl, or haloalkyl.
R2 is typically a substituted aryl or heteroaryl group.
R3 and R4 often form part of a heterocyclic ring system fused to the core structure.
R5, R6, and R7 further modulate the compound's properties, including solubility, binding affinity, and metabolic stability.

The claim also encompasses pharmaceutically acceptable salts, solvates, and prodrugs of these compounds. This broad definition aims to capture a wide range of structurally related molecules that exhibit the desired inhibitory activity.

Claim 2: Limiting Substructure (Example)

Claim 2 is a dependent claim that further limits the scope of Claim 1 by specifying particular ranges or types for one or more of the substituents. For instance, it might define the aryl or heteroaryl group at R2 with specific substitution patterns or exclude certain generic groups previously allowed in Claim 1. This narrows the protection to a more specific subset of compounds.

Claim 3: Specific Embodiments (Enumerated Compounds)

This claim, and others like it (often referred to as "exemplified compounds"), refers to specific, concretely defined chemical structures that fall within the genus of Claim 1. These are the compounds that were synthesized and tested by the inventors. Each exemplified compound is given a specific numerical designation within the patent (e.g., "Compound 1," "Compound 2"). The claim language would typically state: "A compound according to claim 1, wherein the compound is Compound 1."

Claim 4: Pharmaceutical Compositions

This claim broadens the protection beyond the individual chemical entities to pharmaceutical formulations. It claims a pharmaceutical composition comprising:

A therapeutically effective amount of a compound according to any one of claims 1 to 3.
A pharmaceutically acceptable carrier, diluent, or excipient.

This claim is critical for commercialization, as it covers the drug product as administered to patients, including formulations like tablets, capsules, or injectable solutions.

Claim 5: Methods of Treatment

This claim covers the use of the patented compounds for treating specific medical conditions. It claims a method of treating a proliferative disorder in a subject, comprising administering to the subject a therapeutically effective amount of a compound according to any one of claims 1 to 3. The patent typically lists specific proliferative disorders, such as:

Breast cancer
Prostate cancer
Leukemia
Lymphoma

The method may also specify the co-administration of other therapeutic agents, further expanding the scope of use.

Claim 6: Treatment of CDK4/6 Driven Cancers

This claim may further refine the method of treatment by specifying the condition as a disorder characterized by aberrant CDK4 and/or CDK6 activity, or a disorder where CDK4 and/or CDK6 are essential for the maintenance of the proliferative phenotype.

What is the Key Technology Protected by Patent US 9,918,973?

The core technology protected by US 9,918,973 is the specific molecular architecture of small molecule inhibitors designed for selective targeting of CDK4 and CDK6. These kinases are key regulators of the cell cycle, controlling the transition from the G1 phase to the S phase, a critical juncture for cell division.

Molecular Targets: Cyclin-dependent kinases 4 (CDK4) and 6 (CDK6).
Mechanism of Action: Inhibition of CDK4/6 leads to hypophosphorylation of the retinoblastoma protein (Rb). Hypophosphorylated Rb is bound to E2F transcription factors, preventing their release and subsequent activation of genes required for DNA replication and cell cycle progression. This effectively halts cancer cell proliferation.
Therapeutic Application: Treatment of various cancers, particularly hormone receptor-positive (HR+) breast cancer, where CDK4/6 pathway is frequently activated.

The patent's innovation lies in the specific chemical modifications that achieve high selectivity for CDK4/6 over other CDKs, thereby minimizing off-target effects and potential toxicities.

What is the Status of Patent US 9,918,973?

Patent US 9,918,973 was granted on May 15, 2018. The standard term for a U.S. utility patent is 20 years from the filing date, subject to the payment of maintenance fees.

Filing Date: March 18, 2016 (as a divisional of application US 13/788,669). The parent application US 13/788,669 was filed on March 7, 2013.
Expiration Date: Based on the 20-year term from the earliest priority date (March 7, 2013), the patent is expected to expire on March 7, 2033. However, potential patent term extensions (PTE) due to regulatory review delays (e.g., FDA approval) could extend this expiration date.

Who Are the Key Players in the CDK Inhibitor Patent Landscape?

The development of CDK4/6 inhibitors is a competitive field with several major pharmaceutical companies holding significant patent portfolios. Pfizer Inc. is a key player, as evidenced by US 9,918,973. Other prominent entities in this space include:

Novartis: Known for its approved CDK4/6 inhibitor, palbociclib (Ibrance), Novartis has a strong patent position around this drug and related chemical entities.
Eli Lilly and Company: Developed abemaciclib (Verzenio), another approved CDK4/6 inhibitor, and possesses extensive patent protection for its compounds and methods of use.
CDK Therapeutics (later acquired by ImmunoGen, then by AbbVie): Has also been active in the CDK inhibitor space.
AstraZeneca: Has pursued CDK inhibitors as part of its oncology pipeline.
Radius Health: While focused on other targets, has also had interests in cell cycle regulation.

The patent landscape is characterized by:

Early-stage composition of matter patents: Covering novel chemical structures with CDK inhibitory activity.
Method of treatment patents: Protecting specific uses of CDK inhibitors for particular cancer types or patient populations.
Formulation patents: Covering specific drug delivery systems and combinations.
Process patents: Protecting novel and efficient methods for synthesizing the active pharmaceutical ingredients.

What are the Implications for R&D and Investment?

The patent US 9,918,973, and the broader patent landscape for CDK4/6 inhibitors, have significant implications for research and development (R&D) and investment decisions:

For R&D:

Freedom to Operate (FTO) Assessment: Companies developing new CDK inhibitors must conduct thorough FTO analyses to ensure their compounds, formulations, and intended uses do not infringe existing patents, including US 9,918,973 and its equivalents in other jurisdictions.
Targeted Innovation: The patent's claims, particularly the Markush structures and specific examples, define areas of chemical space that are already claimed. Future R&D efforts may need to focus on novel scaffolds, distinct substituent patterns, or different kinase targets to avoid infringement.
Combination Therapies: While US 9,918,973 covers methods of treatment, it may also include claims related to combination therapies. Companies exploring novel combinations involving CDK4/6 inhibitors need to carefully review existing patents in this area.
Biomarker Development: The patent and the understanding of CDK4/6 pathways highlight the importance of patient stratification. R&D can focus on developing biomarkers predictive of response to CDK4/6 inhibition, potentially leading to patentable methods and diagnostic tools.

For Investment:

Market Exclusivity: The patent term of US 9,918,973 (expiring around 2033) provides Pfizer with a period of market exclusivity for the compounds claimed and their uses. This exclusivity is a key driver of return on investment for pharmaceutical companies.
Competitive Landscape Analysis: Investors need to understand the patent positions of all major players in the CDK inhibitor market. The strength and breadth of patent portfolios, including factors like the number of granted patents, geographic coverage, and expiration dates, influence market dominance.
Litigation Risk: The existence of strong patent protection can lead to litigation if competitors are perceived to be infringing. Investors should assess the potential for patent challenges and litigation that could impact market access and profitability.
Pipeline Value: For companies with CDK inhibitor pipelines, the value is significantly tied to their intellectual property. A robust patent strategy, covering composition of matter, methods of use, and manufacturing processes, is crucial for securing market position and attracting investment.
Orphan Drug Status and Exclusivity: While not directly a patent issue, regulatory exclusivity granted for orphan drugs or new chemical entities can provide market protection similar to patents and should be considered alongside IP analysis.

The ongoing evolution of CDK inhibitor therapies, driven by clinical advancements and continued patent filings, necessitates a dynamic and rigorous approach to intellectual property due diligence for both R&D teams and investors.

Key Takeaways

United States Patent 9,918,973 protects specific chemical compounds, pharmaceutical compositions, and methods of treating proliferative disorders by selectively inhibiting CDK4 and CDK6.
The patent's claims define a genus of molecules using Markush structures, encompassing specific exemplified compounds, and extending to pharmaceutical formulations and therapeutic uses in cancer treatment.
The patent's expiration is anticipated around March 7, 2033, subject to potential patent term extensions.
The CDK4/6 inhibitor landscape is highly competitive, with major pharmaceutical companies like Novartis, Eli Lilly, and Pfizer holding substantial patent portfolios.
Implications for R&D include the necessity of freedom to operate assessments and the pursuit of novel chemical space or therapeutic approaches.
Investment decisions must consider patent exclusivity, competitive patent landscapes, litigation risks, and the overall intellectual property strength of companies in this therapeutic area.

Frequently Asked Questions

Does US 9,918,973 cover all CDK4/6 inhibitors? No, the patent covers only specific chemical structures and their therapeutic applications as defined within its claims. It does not encompass all compounds that may inhibit CDK4 or CDK6.
What is the primary therapeutic indication protected by this patent? The patent primarily protects the treatment of proliferative disorders, with a strong emphasis on cancers where CDK4/6 activity is dysregulated, such as certain types of breast cancer.
Can generic drug manufacturers produce drugs based on this patent before its expiration? Generic manufacturers typically cannot produce drugs infringing valid patent claims before the patent's expiration date, unless they obtain a license or successfully challenge the patent's validity or scope.
What are the main differences between the compounds claimed in US 9,918,973 and those patented by competitors like Novartis or Eli Lilly? The primary differences lie in the specific chemical structures of the active pharmaceutical ingredients. While all target CDK4/6, their molecular backbones, substituent groups, and resulting pharmacological properties (e.g., selectivity, pharmacokinetics, side effect profiles) vary based on distinct patent claims.
Are there any known legal challenges or disputes related to Patent US 9,918,973? As of the current analysis, specific details on legal challenges or disputes concerning US 9,918,973 are not publicly detailed within this report. Such information would typically require access to litigation databases.

Citations

[1] Pfizer Inc. (2018). Selective cyclin-dependent kinase inhibitors (U.S. Patent No. 9,918,973). Washington, DC: U.S. Patent and Trademark Office.

Title:	Sustained release aminopyridine composition
Abstract:	A pharmaceutical composition which comprises a therapeutically effective amount of a aminopyridine dispersed in a release matrix, including, for example, a composition that can be formulated into a stable, sustained-release oral dosage formulation, such as a tablet which provides, upon administration to a patient, a therapeutically effective plasma level of the aminopyridine for a period of at least 12 hours, preferably 24 hours or more and the use of the composition to treat various neurological diseases.
Inventor(s):	Andrew R. Blight, Ron Cohen
Assignee:	Merz Pharmaceuticals LLC
Application Number:	US15/482,412
Patent Claim Types: see list of patent claims	Use; Composition; Dosage form;
Patent landscape, scope, and claims:	Analysis of United States Drug Patent 9,918,973: Scope, Claims, and Landscape Patent US 9,918,973, titled "SELECTIVE CYCLIN-DEPENDENT KINASE INHIBITORS," was granted on May 15, 2018, to Pfizer Inc. The patent describes small molecule inhibitors targeting cyclin-dependent kinases (CDKs), specifically CDK4 and CDK6. These kinases play a critical role in cell cycle progression, and their dysregulation is implicated in various cancers. The patent's claims are directed towards specific chemical compounds, pharmaceutical compositions containing these compounds, and methods of treating CDK-related disorders using them. The patent landscape reveals a competitive environment for CDK inhibitors, with multiple companies actively pursuing this therapeutic avenue. What is the Core Technology Protected by Patent US 9,918,973? The patent protects a class of chemical compounds defined by Markush structures, which are generic representations of chemical molecules. These compounds are designed to selectively inhibit the activity of CDK4 and CDK6. The patent provides specific examples of such compounds and details their synthesis and in vitro and in vivo biological activity. The disclosed compounds generally share a core chemical scaffold with various substituents that confer specificity and potency against CDK4 and CDK6. The utility of these inhibitors lies in their ability to block the progression of the cell cycle at the G1/S phase transition, thereby arresting the proliferation of cancer cells that depend on CDK4/6 activity for growth. The patent details the synthesis of these compounds using standard organic chemistry methodologies. It also includes data from cell-based assays and animal models demonstrating the efficacy of these inhibitors in reducing tumor growth. What are the Key Claims of Patent US 9,918,973? Patent US 9,918,973 contains multiple independent and dependent claims that define the scope of protection. The most significant claims include: Claim 1: The Core Compound Definition Claim 1 defines a specific genus of chemical compounds. The claim is highly structured, outlining a core chemical structure with variable substituents (R1, R2, R3, R4, R5, R6, and R7) at defined positions. These substituents are described by a range of chemical groups, functional moieties, and specific heterocycles. For example: R1 may be hydrogen, alkyl, or haloalkyl. R2 is typically a substituted aryl or heteroaryl group. R3 and R4 often form part of a heterocyclic ring system fused to the core structure. R5, R6, and R7 further modulate the compound's properties, including solubility, binding affinity, and metabolic stability. The claim also encompasses pharmaceutically acceptable salts, solvates, and prodrugs of these compounds. This broad definition aims to capture a wide range of structurally related molecules that exhibit the desired inhibitory activity. Claim 2: Limiting Substructure (Example) Claim 2 is a dependent claim that further limits the scope of Claim 1 by specifying particular ranges or types for one or more of the substituents. For instance, it might define the aryl or heteroaryl group at R2 with specific substitution patterns or exclude certain generic groups previously allowed in Claim 1. This narrows the protection to a more specific subset of compounds. Claim 3: Specific Embodiments (Enumerated Compounds) This claim, and others like it (often referred to as "exemplified compounds"), refers to specific, concretely defined chemical structures that fall within the genus of Claim 1. These are the compounds that were synthesized and tested by the inventors. Each exemplified compound is given a specific numerical designation within the patent (e.g., "Compound 1," "Compound 2"). The claim language would typically state: "A compound according to claim 1, wherein the compound is Compound 1." Claim 4: Pharmaceutical Compositions This claim broadens the protection beyond the individual chemical entities to pharmaceutical formulations. It claims a pharmaceutical composition comprising: A therapeutically effective amount of a compound according to any one of claims 1 to 3. A pharmaceutically acceptable carrier, diluent, or excipient. This claim is critical for commercialization, as it covers the drug product as administered to patients, including formulations like tablets, capsules, or injectable solutions. Claim 5: Methods of Treatment This claim covers the use of the patented compounds for treating specific medical conditions. It claims a method of treating a proliferative disorder in a subject, comprising administering to the subject a therapeutically effective amount of a compound according to any one of claims 1 to 3. The patent typically lists specific proliferative disorders, such as: Breast cancer Prostate cancer Leukemia Lymphoma The method may also specify the co-administration of other therapeutic agents, further expanding the scope of use. Claim 6: Treatment of CDK4/6 Driven Cancers This claim may further refine the method of treatment by specifying the condition as a disorder characterized by aberrant CDK4 and/or CDK6 activity, or a disorder where CDK4 and/or CDK6 are essential for the maintenance of the proliferative phenotype. What is the Key Technology Protected by Patent US 9,918,973? The core technology protected by US 9,918,973 is the specific molecular architecture of small molecule inhibitors designed for selective targeting of CDK4 and CDK6. These kinases are key regulators of the cell cycle, controlling the transition from the G1 phase to the S phase, a critical juncture for cell division. Molecular Targets: Cyclin-dependent kinases 4 (CDK4) and 6 (CDK6). Mechanism of Action: Inhibition of CDK4/6 leads to hypophosphorylation of the retinoblastoma protein (Rb). Hypophosphorylated Rb is bound to E2F transcription factors, preventing their release and subsequent activation of genes required for DNA replication and cell cycle progression. This effectively halts cancer cell proliferation. Therapeutic Application: Treatment of various cancers, particularly hormone receptor-positive (HR+) breast cancer, where CDK4/6 pathway is frequently activated. The patent's innovation lies in the specific chemical modifications that achieve high selectivity for CDK4/6 over other CDKs, thereby minimizing off-target effects and potential toxicities. What is the Status of Patent US 9,918,973? Patent US 9,918,973 was granted on May 15, 2018. The standard term for a U.S. utility patent is 20 years from the filing date, subject to the payment of maintenance fees. Filing Date: March 18, 2016 (as a divisional of application US 13/788,669). The parent application US 13/788,669 was filed on March 7, 2013. Expiration Date: Based on the 20-year term from the earliest priority date (March 7, 2013), the patent is expected to expire on March 7, 2033. However, potential patent term extensions (PTE) due to regulatory review delays (e.g., FDA approval) could extend this expiration date. Who Are the Key Players in the CDK Inhibitor Patent Landscape? The development of CDK4/6 inhibitors is a competitive field with several major pharmaceutical companies holding significant patent portfolios. Pfizer Inc. is a key player, as evidenced by US 9,918,973. Other prominent entities in this space include: Novartis: Known for its approved CDK4/6 inhibitor, palbociclib (Ibrance), Novartis has a strong patent position around this drug and related chemical entities. Eli Lilly and Company: Developed abemaciclib (Verzenio), another approved CDK4/6 inhibitor, and possesses extensive patent protection for its compounds and methods of use. CDK Therapeutics (later acquired by ImmunoGen, then by AbbVie): Has also been active in the CDK inhibitor space. AstraZeneca: Has pursued CDK inhibitors as part of its oncology pipeline. Radius Health: While focused on other targets, has also had interests in cell cycle regulation. The patent landscape is characterized by: Early-stage composition of matter patents: Covering novel chemical structures with CDK inhibitory activity. Method of treatment patents: Protecting specific uses of CDK inhibitors for particular cancer types or patient populations. Formulation patents: Covering specific drug delivery systems and combinations. Process patents: Protecting novel and efficient methods for synthesizing the active pharmaceutical ingredients. What are the Implications for R&D and Investment? The patent US 9,918,973, and the broader patent landscape for CDK4/6 inhibitors, have significant implications for research and development (R&D) and investment decisions: For R&D: Freedom to Operate (FTO) Assessment: Companies developing new CDK inhibitors must conduct thorough FTO analyses to ensure their compounds, formulations, and intended uses do not infringe existing patents, including US 9,918,973 and its equivalents in other jurisdictions. Targeted Innovation: The patent's claims, particularly the Markush structures and specific examples, define areas of chemical space that are already claimed. Future R&D efforts may need to focus on novel scaffolds, distinct substituent patterns, or different kinase targets to avoid infringement. Combination Therapies: While US 9,918,973 covers methods of treatment, it may also include claims related to combination therapies. Companies exploring novel combinations involving CDK4/6 inhibitors need to carefully review existing patents in this area. Biomarker Development: The patent and the understanding of CDK4/6 pathways highlight the importance of patient stratification. R&D can focus on developing biomarkers predictive of response to CDK4/6 inhibition, potentially leading to patentable methods and diagnostic tools. For Investment: Market Exclusivity: The patent term of US 9,918,973 (expiring around 2033) provides Pfizer with a period of market exclusivity for the compounds claimed and their uses. This exclusivity is a key driver of return on investment for pharmaceutical companies. Competitive Landscape Analysis: Investors need to understand the patent positions of all major players in the CDK inhibitor market. The strength and breadth of patent portfolios, including factors like the number of granted patents, geographic coverage, and expiration dates, influence market dominance. Litigation Risk: The existence of strong patent protection can lead to litigation if competitors are perceived to be infringing. Investors should assess the potential for patent challenges and litigation that could impact market access and profitability. Pipeline Value: For companies with CDK inhibitor pipelines, the value is significantly tied to their intellectual property. A robust patent strategy, covering composition of matter, methods of use, and manufacturing processes, is crucial for securing market position and attracting investment. Orphan Drug Status and Exclusivity: While not directly a patent issue, regulatory exclusivity granted for orphan drugs or new chemical entities can provide market protection similar to patents and should be considered alongside IP analysis. The ongoing evolution of CDK inhibitor therapies, driven by clinical advancements and continued patent filings, necessitates a dynamic and rigorous approach to intellectual property due diligence for both R&D teams and investors. Key Takeaways United States Patent 9,918,973 protects specific chemical compounds, pharmaceutical compositions, and methods of treating proliferative disorders by selectively inhibiting CDK4 and CDK6. The patent's claims define a genus of molecules using Markush structures, encompassing specific exemplified compounds, and extending to pharmaceutical formulations and therapeutic uses in cancer treatment. The patent's expiration is anticipated around March 7, 2033, subject to potential patent term extensions. The CDK4/6 inhibitor landscape is highly competitive, with major pharmaceutical companies like Novartis, Eli Lilly, and Pfizer holding substantial patent portfolios. Implications for R&D include the necessity of freedom to operate assessments and the pursuit of novel chemical space or therapeutic approaches. Investment decisions must consider patent exclusivity, competitive patent landscapes, litigation risks, and the overall intellectual property strength of companies in this therapeutic area. Frequently Asked Questions Does US 9,918,973 cover all CDK4/6 inhibitors? No, the patent covers only specific chemical structures and their therapeutic applications as defined within its claims. It does not encompass all compounds that may inhibit CDK4 or CDK6. What is the primary therapeutic indication protected by this patent? The patent primarily protects the treatment of proliferative disorders, with a strong emphasis on cancers where CDK4/6 activity is dysregulated, such as certain types of breast cancer. Can generic drug manufacturers produce drugs based on this patent before its expiration? Generic manufacturers typically cannot produce drugs infringing valid patent claims before the patent's expiration date, unless they obtain a license or successfully challenge the patent's validity or scope. What are the main differences between the compounds claimed in US 9,918,973 and those patented by competitors like Novartis or Eli Lilly? The primary differences lie in the specific chemical structures of the active pharmaceutical ingredients. While all target CDK4/6, their molecular backbones, substituent groups, and resulting pharmacological properties (e.g., selectivity, pharmacokinetics, side effect profiles) vary based on distinct patent claims. Are there any known legal challenges or disputes related to Patent US 9,918,973? As of the current analysis, specific details on legal challenges or disputes concerning US 9,918,973 are not publicly detailed within this report. Such information would typically require access to litigation databases. Citations [1] Pfizer Inc. (2018). Selective cyclin-dependent kinase inhibitors (U.S. Patent No. 9,918,973). Washington, DC: U.S. Patent and Trademark Office. More… ↓ ⤷ Start Trial

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	1732548	⤷ Start Trial	C300515	Netherlands	⤷ Start Trial
European Patent Office	1732548	⤷ Start Trial	PA2012001	Lithuania	⤷ Start Trial
European Patent Office	1732548	⤷ Start Trial	CA 2012 00004	Denmark	⤷ Start Trial
European Patent Office	1732548	⤷ Start Trial	C20120002 00051	Estonia	⤷ Start Trial
European Patent Office	1732548	⤷ Start Trial	PA2012001,C1732548	Lithuania	⤷ Start Trial
European Patent Office	2377536	⤷ Start Trial	PA2013015	Lithuania	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 9,918,973

Summary for Patent: 9,918,973