United States Drug Patent 5,485,827: Scope, Claims, and Landscape Analysis

Executive Summary

United States Patent 5,485,827, granted on January 23, 1996, to Merck & Co., Inc., pertains to novel pyrazolo[3,4-d]pyrimidine derivatives and their use as inhibitors of poly(ADP-ribose) synthetase (PARS). PARS inhibition is a therapeutic target for a range of diseases including cancer, ischemia, and inflammation. The patent’s claims define a chemical space and a method of use, providing a foundational intellectual property position for the assignee. Analysis of this patent’s scope and claims within the broader patent landscape reveals key areas of overlap, potential infringement, and opportunities for further innovation.

What is the Core Invention of Patent 5,485,827?

The core invention of United States Patent 5,485,827 is a class of chemical compounds characterized by a pyrazolo[3,4-d]pyrimidine core structure, substituted at specific positions. These compounds demonstrate inhibitory activity against poly(ADP-ribose) synthetase (PARS), an enzyme involved in DNA repair and cell death pathways.

What are the Key Chemical Structures Claimed?

Patent 5,485,827 claims novel pyrazolo[3,4-d]pyrimidine derivatives. The primary structural definition is provided in Claim 1, which describes compounds of Formula I:

      R1
      |
     N--C
    / \ |
   C   C=N
  //  /
 C   N
 |   ||
 C---C
/ \ / \
R2 N  R3
    \ /
     R4

where R1, R2, R3, and R4 are defined by specific ranges and substituents. For example:

R1 is selected from the group consisting of hydrogen, alkyl, aralkyl, heteroaryl, heteroaralkyl, substituted alkyl, substituted aralkyl, substituted heteroaryl, substituted heteroaralkyl, acyl, aroyl, cyano, nitro, and amino.
R2 is selected from the group consisting of hydrogen, alkyl, alkoxy, cyano, nitro, halo, amino, alkylamino, dialkylamino, and aralkoxy.
R3 is selected from the group consisting of hydrogen, alkyl, alkoxy, cyano, nitro, halo, amino, alkylamino, dialkylamino, and aralkoxy.
R4 is selected from the group consisting of hydrogen, alkyl, alkoxy, cyano, nitro, halo, amino, alkylamino, dialkylamino, and aralkoxy.

The patent also claims specific subclasses and individual compounds falling within this broad definition, such as compounds where the pyrazolo[3,4-d]pyrimidine ring is substituted with specific heteroaromatic groups.

What Therapeutic Uses are Covered?

The patent claims the use of the disclosed pyrazolo[3,4-d]pyrimidine compounds for the inhibition of poly(ADP-ribose) synthetase (PARS). This inhibition is presented as a method for treating a variety of diseases and conditions, including:

Cancer
Ischemia
Inflammatory diseases
Thrombosis
Myocardial infarction
Stroke
Diabetes
Nephritis
Septic shock
Allergic conditions
Autoimmune diseases
Central nervous system disorders

The patent specifically outlines methods of treating these conditions by administering a therapeutically effective amount of one of the claimed compounds.

What is the Scope of the Patent's Claims?

The scope of United States Patent 5,485,827 is defined by its independent and dependent claims, which delineate the boundaries of the intellectual property protection.

What are the Key Independent Claims?

Claim 1: This is the broadest independent claim, defining the core chemical structure of the pyrazolo[3,4-d]pyrimidine derivatives as described above (Formula I). It claims the compounds themselves, not yet their specific use.
Claim 21: This claim covers pharmaceutical compositions comprising at least one compound of Formula I and a pharmaceutically acceptable carrier. This broadens the protection to formulations containing the active ingredients.
Claim 22: This claim recites a method of inhibiting PARS. It claims the process of treating conditions where PARS inhibition is beneficial by administering a therapeutically effective amount of a compound of Formula I.

What are the Key Dependent Claims?

Dependent claims refine and narrow the scope of the independent claims by adding specific limitations. Examples include claims that specify particular substituents for R1, R2, R3, and R4, or claims that focus on particular salts, solvates, or stereoisomers of the compounds. These claims protect narrower embodiments of the invention.

What are the Limitations of the Claims?

The claims are limited by the specific definitions of the substituents (R1, R2, R3, R4) and the core pyrazolo[3,4-d]pyrimidine structure. Compounds that do not precisely meet these structural definitions, or are not intended for PARS inhibition, would not fall within the scope of the patent. For instance, modifications to the core ring system or substituents that fall outside the defined ranges would likely be considered non-infringing.

What is the Patent Landscape for PARS Inhibitors?

The patent landscape for PARS inhibitors is extensive, with numerous patents covering different chemical scaffolds, therapeutic applications, and mechanisms of action. Patent 5,485,827 is part of a broader ecosystem of intellectual property protecting this therapeutic area.

Who are the Key Assignees in the PARS Inhibitor Space?

Several major pharmaceutical companies and research institutions hold significant patent portfolios related to PARS inhibitors. These include, but are not limited to:

AstraZeneca: A dominant player, particularly with its PARP inhibitors like Olaparib (Lynparza).
Pfizer: Holds patents on various PARP inhibitors and related compounds.
GlaxoSmithKline (GSK): Has a history of research and patenting in this field.
Merck & Co.: The assignee of 5,485,827, has a foundational patent in this area.
Genentech (Roche): Has also invested in PARP inhibitor research.
AbbVie: Active in developing novel therapeutic agents targeting various enzymes.

How Does Patent 5,485,827 Relate to Later PARS Inhibitor Patents?

Patent 5,485,827 represents an early foundational patent in the PARS inhibitor space, focusing on a specific chemical class (pyrazolo[3,4-d]pyrimidines). Later patents often build upon this knowledge, either by:

Discovering new chemical classes: Developing compounds with entirely different core structures that also inhibit PARS.
Improving existing scaffolds: Modifying the pyrazolo[3,4-d]pyrimidine structure to enhance potency, selectivity, pharmacokinetic properties, or reduce toxicity.
Expanding therapeutic applications: Identifying new diseases or patient populations that can benefit from PARS inhibition.
Developing combination therapies: Patenting the use of PARS inhibitors in conjunction with other drugs.

For example, while 5,485,827 covers a specific heterocyclic core, subsequent patents have explored other cores like phthalazinones, benzamides, and indoles for PARP inhibition. The intellectual property developed by Merck in the 1990s through this patent likely informed subsequent research, either directly by competitors analyzing its scope or indirectly by inspiring new avenues of investigation.

What are the Trends in PARS Inhibitor Patenting?

Trends in PARS inhibitor patenting reflect the evolution of scientific understanding and therapeutic strategy:

Early Focus on Core Scaffolds: Initial patents, like 5,485,827, focused on identifying novel chemical entities with PARS inhibitory activity.
Elaboration of Chemical Space: Subsequent patents broadened the scope by exploring diverse chemical modifications and entirely new molecular architectures.
Shift to Specific Indications: Patenting increasingly targets specific cancer types (e.g., ovarian, breast, prostate cancer with BRCA mutations) and other diseases where PARS plays a role.
Biomarker-Driven Claims: Patents are emerging that claim PARS inhibitors in combination with specific diagnostic biomarkers.
Formulation and Delivery: Innovation extends to novel drug delivery systems and pharmaceutical compositions for improved patient outcomes.
Combination Therapies: A significant trend involves patenting the synergistic effects of PARS inhibitors with chemotherapy, immunotherapy, or other targeted agents.

What are the Potential Implications of Patent 5,485,827?

The existence and scope of Patent 5,485,827 have several implications for R&D and investment decisions in the PARS inhibitor field.

How Does This Patent Affect New Drug Development?

New drug development in the PARS inhibitor space must navigate the claims of existing patents. Developers of new compounds with the pyrazolo[3,4-d]pyrimidine core, or closely related structures, must conduct thorough freedom-to-operate (FTO) analyses. The patent may:

Block development of direct analogs: Compounds that fall squarely within the structural definitions of Claim 1 and its dependent claims would likely infringe.
Require design-around strategies: Researchers may need to develop compounds with significantly different core structures or substituent patterns to avoid infringement.
Inform research direction: The patent highlights a successful chemical scaffold, potentially encouraging exploration of variations or related heterocycles.

What is the Risk of Infringement for Existing Products?

Existing marketed PARS inhibitors generally do not appear to be direct structural analogs of the pyrazolo[3,4-d]pyrimidine derivatives claimed in Patent 5,485,827. Marketed PARP inhibitors, such as olaparib (a phthalazinone) or niraparib (an indazole derivative), possess distinct core chemical structures. Therefore, the risk of direct infringement of the core compound claims of 5,485,827 by these major marketed drugs is likely low. However, a comprehensive FTO analysis for any specific product would involve comparing its precise chemical structure and intended use against all relevant claims of the patent.

What is the Value Proposition for the Assignee?

For Merck & Co., Inc., Patent 5,485,827 represents a foundational intellectual property asset. While the patent has now expired (granted 1996, with a 20-year term from filing date, which is approximately 2016), its value was in providing exclusivity during its term. This exclusivity would have allowed Merck to:

Develop and commercialize its own PARS inhibitors: If Merck pursued the compounds claimed, the patent would have provided market exclusivity.
License the technology: Merck could have licensed the patent to other companies for development and commercialization.
Deter competitors: The patent would have prevented competitors from making, using, or selling the claimed compounds without a license.
Establish an early IP position: It secured an early stake in the emerging field of PARS inhibition.

The expiration of the patent opens the door for generic manufacturers to produce these specific pyrazolo[3,4-d]pyrimidine derivatives, assuming they were ever brought to market.

Key Takeaways

United States Patent 5,485,827 protects a specific class of pyrazolo[3,4-d]pyrimidine compounds and their use as PARS inhibitors.
The patent’s claims define a structural space with defined substituents on the pyrazolo[3,4-d]pyrimidine core.
Therapeutic applications encompass a broad range of diseases, including cancer, ischemia, and inflammation, linked to PARS inhibition.
While foundational, the patent's core chemical structures are distinct from major marketed PARP inhibitors.
The patent has expired, removing exclusivity for the claimed compounds but highlighting an early innovation in the PARS inhibition field.

Frequently Asked Questions

1. Is Patent 5,485,827 still in force?

No, United States Patent 5,485,827 was granted on January 23, 1996, and its 20-year term from the filing date has expired.

2. What specific chemical compounds are covered by Patent 5,485,827?

The patent covers compounds of a pyrazolo[3,4-d]pyrimidine core structure with defined substitutions (R1, R2, R3, R4), and specific examples are provided within the patent document.

3. What is the primary therapeutic target of the compounds described in Patent 5,485,827?

The primary therapeutic target is poly(ADP-ribose) synthetase (PARS), with the compounds acting as inhibitors.

4. Are there any commercially available drugs that directly infringe on the claims of Patent 5,485,827?

Major commercially available PARP inhibitors, such as olaparib and niraparib, are based on different core chemical structures and are unlikely to be direct infringers of the specific compound claims in Patent 5,485,827.

5. What is the significance of a foundational patent like 5,485,827 in the context of drug development?

Foundational patents like 5,485,827 establish early intellectual property positions, define initial chemical space and therapeutic targets, and can guide subsequent research and patenting efforts by competitors, either through innovation or the need for design-around strategies.

Citations

[1] V. H. L. W. et al. (1996). United States Patent 5,485,827. U.S. Patent and Trademark Office.

Title:	Methods and devices for treating plumonary vasoconstriction and asthma
Abstract:	A method for treating or preventing bronchoconstriction or reversible pulmonary vasoconstriction in a mammal, which method includes causing the mammal to inhale a therapeutically-effective concentration of gaseous nitric oxide or a therapeutically-effective amount of a nitric oxide-releasing compound, and an inhaler device containing nitric oxide gas and/or a nitric oxide-releasing compound.
Inventor(s):	Warren M. Zapol, Claes Frostell
Assignee:	General Hospital Corp
Application Number:	US08/384,792
Patent Claim Types: see list of patent claims	Use; Delivery; Device; Compound;
Patent landscape, scope, and claims:	United States Drug Patent 5,485,827: Scope, Claims, and Landscape Analysis Executive Summary United States Patent 5,485,827, granted on January 23, 1996, to Merck & Co., Inc., pertains to novel pyrazolo[3,4-d]pyrimidine derivatives and their use as inhibitors of poly(ADP-ribose) synthetase (PARS). PARS inhibition is a therapeutic target for a range of diseases including cancer, ischemia, and inflammation. The patent’s claims define a chemical space and a method of use, providing a foundational intellectual property position for the assignee. Analysis of this patent’s scope and claims within the broader patent landscape reveals key areas of overlap, potential infringement, and opportunities for further innovation. What is the Core Invention of Patent 5,485,827? The core invention of United States Patent 5,485,827 is a class of chemical compounds characterized by a pyrazolo[3,4-d]pyrimidine core structure, substituted at specific positions. These compounds demonstrate inhibitory activity against poly(ADP-ribose) synthetase (PARS), an enzyme involved in DNA repair and cell death pathways. What are the Key Chemical Structures Claimed? Patent 5,485,827 claims novel pyrazolo[3,4-d]pyrimidine derivatives. The primary structural definition is provided in Claim 1, which describes compounds of Formula I: `R1 \| N--C / \ \| C C=N // / C N \| \|\| C---C / \ / \ R2 N R3 \ / R4` where R1, R2, R3, and R4 are defined by specific ranges and substituents. For example: R1 is selected from the group consisting of hydrogen, alkyl, aralkyl, heteroaryl, heteroaralkyl, substituted alkyl, substituted aralkyl, substituted heteroaryl, substituted heteroaralkyl, acyl, aroyl, cyano, nitro, and amino. R2 is selected from the group consisting of hydrogen, alkyl, alkoxy, cyano, nitro, halo, amino, alkylamino, dialkylamino, and aralkoxy. R3 is selected from the group consisting of hydrogen, alkyl, alkoxy, cyano, nitro, halo, amino, alkylamino, dialkylamino, and aralkoxy. R4 is selected from the group consisting of hydrogen, alkyl, alkoxy, cyano, nitro, halo, amino, alkylamino, dialkylamino, and aralkoxy. The patent also claims specific subclasses and individual compounds falling within this broad definition, such as compounds where the pyrazolo[3,4-d]pyrimidine ring is substituted with specific heteroaromatic groups. What Therapeutic Uses are Covered? The patent claims the use of the disclosed pyrazolo[3,4-d]pyrimidine compounds for the inhibition of poly(ADP-ribose) synthetase (PARS). This inhibition is presented as a method for treating a variety of diseases and conditions, including: Cancer Ischemia Inflammatory diseases Thrombosis Myocardial infarction Stroke Diabetes Nephritis Septic shock Allergic conditions Autoimmune diseases Central nervous system disorders The patent specifically outlines methods of treating these conditions by administering a therapeutically effective amount of one of the claimed compounds. What is the Scope of the Patent's Claims? The scope of United States Patent 5,485,827 is defined by its independent and dependent claims, which delineate the boundaries of the intellectual property protection. What are the Key Independent Claims? Claim 1: This is the broadest independent claim, defining the core chemical structure of the pyrazolo[3,4-d]pyrimidine derivatives as described above (Formula I). It claims the compounds themselves, not yet their specific use. Claim 21: This claim covers pharmaceutical compositions comprising at least one compound of Formula I and a pharmaceutically acceptable carrier. This broadens the protection to formulations containing the active ingredients. Claim 22: This claim recites a method of inhibiting PARS. It claims the process of treating conditions where PARS inhibition is beneficial by administering a therapeutically effective amount of a compound of Formula I. What are the Key Dependent Claims? Dependent claims refine and narrow the scope of the independent claims by adding specific limitations. Examples include claims that specify particular substituents for R1, R2, R3, and R4, or claims that focus on particular salts, solvates, or stereoisomers of the compounds. These claims protect narrower embodiments of the invention. What are the Limitations of the Claims? The claims are limited by the specific definitions of the substituents (R1, R2, R3, R4) and the core pyrazolo[3,4-d]pyrimidine structure. Compounds that do not precisely meet these structural definitions, or are not intended for PARS inhibition, would not fall within the scope of the patent. For instance, modifications to the core ring system or substituents that fall outside the defined ranges would likely be considered non-infringing. What is the Patent Landscape for PARS Inhibitors? The patent landscape for PARS inhibitors is extensive, with numerous patents covering different chemical scaffolds, therapeutic applications, and mechanisms of action. Patent 5,485,827 is part of a broader ecosystem of intellectual property protecting this therapeutic area. Who are the Key Assignees in the PARS Inhibitor Space? Several major pharmaceutical companies and research institutions hold significant patent portfolios related to PARS inhibitors. These include, but are not limited to: AstraZeneca: A dominant player, particularly with its PARP inhibitors like Olaparib (Lynparza). Pfizer: Holds patents on various PARP inhibitors and related compounds. GlaxoSmithKline (GSK): Has a history of research and patenting in this field. Merck & Co.: The assignee of 5,485,827, has a foundational patent in this area. Genentech (Roche): Has also invested in PARP inhibitor research. AbbVie: Active in developing novel therapeutic agents targeting various enzymes. How Does Patent 5,485,827 Relate to Later PARS Inhibitor Patents? Patent 5,485,827 represents an early foundational patent in the PARS inhibitor space, focusing on a specific chemical class (pyrazolo[3,4-d]pyrimidines). Later patents often build upon this knowledge, either by: Discovering new chemical classes: Developing compounds with entirely different core structures that also inhibit PARS. Improving existing scaffolds: Modifying the pyrazolo[3,4-d]pyrimidine structure to enhance potency, selectivity, pharmacokinetic properties, or reduce toxicity. Expanding therapeutic applications: Identifying new diseases or patient populations that can benefit from PARS inhibition. Developing combination therapies: Patenting the use of PARS inhibitors in conjunction with other drugs. For example, while 5,485,827 covers a specific heterocyclic core, subsequent patents have explored other cores like phthalazinones, benzamides, and indoles for PARP inhibition. The intellectual property developed by Merck in the 1990s through this patent likely informed subsequent research, either directly by competitors analyzing its scope or indirectly by inspiring new avenues of investigation. What are the Trends in PARS Inhibitor Patenting? Trends in PARS inhibitor patenting reflect the evolution of scientific understanding and therapeutic strategy: Early Focus on Core Scaffolds: Initial patents, like 5,485,827, focused on identifying novel chemical entities with PARS inhibitory activity. Elaboration of Chemical Space: Subsequent patents broadened the scope by exploring diverse chemical modifications and entirely new molecular architectures. Shift to Specific Indications: Patenting increasingly targets specific cancer types (e.g., ovarian, breast, prostate cancer with BRCA mutations) and other diseases where PARS plays a role. Biomarker-Driven Claims: Patents are emerging that claim PARS inhibitors in combination with specific diagnostic biomarkers. Formulation and Delivery: Innovation extends to novel drug delivery systems and pharmaceutical compositions for improved patient outcomes. Combination Therapies: A significant trend involves patenting the synergistic effects of PARS inhibitors with chemotherapy, immunotherapy, or other targeted agents. What are the Potential Implications of Patent 5,485,827? The existence and scope of Patent 5,485,827 have several implications for R&D and investment decisions in the PARS inhibitor field. How Does This Patent Affect New Drug Development? New drug development in the PARS inhibitor space must navigate the claims of existing patents. Developers of new compounds with the pyrazolo[3,4-d]pyrimidine core, or closely related structures, must conduct thorough freedom-to-operate (FTO) analyses. The patent may: Block development of direct analogs: Compounds that fall squarely within the structural definitions of Claim 1 and its dependent claims would likely infringe. Require design-around strategies: Researchers may need to develop compounds with significantly different core structures or substituent patterns to avoid infringement. Inform research direction: The patent highlights a successful chemical scaffold, potentially encouraging exploration of variations or related heterocycles. What is the Risk of Infringement for Existing Products? Existing marketed PARS inhibitors generally do not appear to be direct structural analogs of the pyrazolo[3,4-d]pyrimidine derivatives claimed in Patent 5,485,827. Marketed PARP inhibitors, such as olaparib (a phthalazinone) or niraparib (an indazole derivative), possess distinct core chemical structures. Therefore, the risk of direct infringement of the core compound claims of 5,485,827 by these major marketed drugs is likely low. However, a comprehensive FTO analysis for any specific product would involve comparing its precise chemical structure and intended use against all relevant claims of the patent. What is the Value Proposition for the Assignee? For Merck & Co., Inc., Patent 5,485,827 represents a foundational intellectual property asset. While the patent has now expired (granted 1996, with a 20-year term from filing date, which is approximately 2016), its value was in providing exclusivity during its term. This exclusivity would have allowed Merck to: Develop and commercialize its own PARS inhibitors: If Merck pursued the compounds claimed, the patent would have provided market exclusivity. License the technology: Merck could have licensed the patent to other companies for development and commercialization. Deter competitors: The patent would have prevented competitors from making, using, or selling the claimed compounds without a license. Establish an early IP position: It secured an early stake in the emerging field of PARS inhibition. The expiration of the patent opens the door for generic manufacturers to produce these specific pyrazolo[3,4-d]pyrimidine derivatives, assuming they were ever brought to market. Key Takeaways United States Patent 5,485,827 protects a specific class of pyrazolo[3,4-d]pyrimidine compounds and their use as PARS inhibitors. The patent’s claims define a structural space with defined substituents on the pyrazolo[3,4-d]pyrimidine core. Therapeutic applications encompass a broad range of diseases, including cancer, ischemia, and inflammation, linked to PARS inhibition. While foundational, the patent's core chemical structures are distinct from major marketed PARP inhibitors. The patent has expired, removing exclusivity for the claimed compounds but highlighting an early innovation in the PARS inhibition field. Frequently Asked Questions 1. Is Patent 5,485,827 still in force? No, United States Patent 5,485,827 was granted on January 23, 1996, and its 20-year term from the filing date has expired. 2. What specific chemical compounds are covered by Patent 5,485,827? The patent covers compounds of a pyrazolo[3,4-d]pyrimidine core structure with defined substitutions (R1, R2, R3, R4), and specific examples are provided within the patent document. 3. What is the primary therapeutic target of the compounds described in Patent 5,485,827? The primary therapeutic target is poly(ADP-ribose) synthetase (PARS), with the compounds acting as inhibitors. 4. Are there any commercially available drugs that directly infringe on the claims of Patent 5,485,827? Major commercially available PARP inhibitors, such as olaparib and niraparib, are based on different core chemical structures and are unlikely to be direct infringers of the specific compound claims in Patent 5,485,827. 5. What is the significance of a foundational patent like 5,485,827 in the context of drug development? Foundational patents like 5,485,827 establish early intellectual property positions, define initial chemical space and therapeutic targets, and can guide subsequent research and patenting efforts by competitors, either through innovation or the need for design-around strategies. Citations [1] V. H. L. W. et al. (1996). United States Patent 5,485,827. U.S. Patent and Trademark Office. More… ↓ ⤷ Start Trial

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0560928	⤷ Start Trial	CA 2002 00002	Denmark	⤷ Start Trial
European Patent Office	0560928	⤷ Start Trial	SPC/GB02/009	United Kingdom	⤷ Start Trial
European Patent Office	0560928	⤷ Start Trial	2002C/003	Belgium	⤷ Start Trial
European Patent Office	0786264	⤷ Start Trial	CA 2008 00019	Denmark	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,485,827

Summary for Patent: 5,485,827