United States Patent 6,635,278: Fused 1,2-Diazines as Factor Xa Inhibitors

This analysis details United States Patent 6,635,278, covering a class of fused 1,2-diazine compounds and their use as Factor Xa inhibitors. The patent, granted on October 19, 2003, to Bristol-Myers Squibb Company, describes specific chemical structures, their synthesis, and their therapeutic applications, primarily in preventing or treating thrombotic disorders.

What Does Patent 6,635,278 Claim?

What are the core chemical structures claimed in the patent?

The patent claims a genus of fused 1,2-diazines. Specifically, it claims compounds of Formula I:

      R1
      |
  N---N
 / \ / \
R5--C---C--R2
    |   |
    C---C--R3
   / \ /
  R4  C=C
      |
      R6

where R1, R2, R3, R4, R5, and R6 are defined by specific chemical groups and substitutions. These groups include, but are not limited to, substituted aryl, heteroaryl, alkyl, alkoxy, amino, and haloalkyl moieties. The patent details numerous specific examples of compounds falling within this general formula, illustrating variations in substituents at different positions to achieve Factor Xa inhibitory activity.

The patent also claims pharmaceutically acceptable salts, prodrugs, solvates, and hydrates of these compounds.

What is the claimed therapeutic use of these compounds?

The primary therapeutic use claimed is the inhibition of Factor Xa (FXa). FXa is a serine protease that plays a critical role in the coagulation cascade, ultimately leading to the formation of thrombin and fibrin, which are essential for blood clot formation. Inhibiting FXa is a well-established strategy for preventing and treating thrombotic events.

The patent claims methods of treating or preventing thrombotic disorders. These disorders include, but are not limited to:

Deep vein thrombosis (DVT)
Pulmonary embolism (PE)
Atrial fibrillation-related thromboembolism
Myocardial infarction (heart attack)
Stroke
Disseminated intravascular coagulation (DIC)

The claimed methods involve administering a therapeutically effective amount of a compound of Formula I or a pharmaceutically acceptable salt, prodrug, solvate, or hydrate thereof.

What are the key Markush groups and substituents defined?

The patent defines broad categories of substituents (Markush groups) for R1 through R6. These definitions are crucial for understanding the scope of the claims. Examples of substituent types include:

R1: Typically hydrogen, alkyl, substituted alkyl, alkoxy, or acyl.
R2: Often aryl or heteroaryl groups, which can be further substituted with various groups such as halogens, alkyls, alkoxy, cyano, nitro, or amino.
R3: Can be hydrogen, alkyl, substituted alkyl, or connected to form a fused ring system.
R4: Similar to R3, can be hydrogen, alkyl, or participate in fused ring structures.
R5: Commonly hydrogen, alkyl, or substituted alkyl.
R6: Frequently hydrogen, alkyl, substituted alkyl, aryl, or heteroaryl.

The specific combinations and allowed substitutions are detailed across numerous sub-claims, providing a granular view of the patented chemical space. For instance, a claim might specify that if R2 is an aryl group, it must be substituted with a halogen at a particular position.

What are the claimed methods of synthesis?

The patent provides detailed synthetic procedures for preparing the claimed compounds. These methods generally involve multi-step organic synthesis, employing standard chemical reactions. Typical steps might include:

Heterocycle formation: Cyclization reactions to construct the fused 1,2-diazine core.
Functional group interconversions: Modification of existing groups through oxidation, reduction, or substitution.
Coupling reactions: Carbon-carbon or carbon-heteroatom bond formation using reagents like palladium catalysts.
Amidation or esterification: Introduction of amide or ester functionalities.

Specific synthetic schemes and examples are provided, outlining reaction conditions, reagents, yields, and purification methods for numerous representative compounds. These details are critical for practicing the invention and for assessing potential infringement.

What is the patent landscape surrounding Factor Xa inhibitors?

Who are the key competitors and their patent portfolios?

The landscape of Factor Xa inhibitors is highly competitive, with several major pharmaceutical companies holding significant patent portfolios. Key players include:

Bayer AG: Known for Xarelto (rivaroxaban). Bayer has a substantial patent portfolio covering rivaroxaban and related compounds, including its synthesis and therapeutic uses.
Bristol-Myers Squibb Company: The assignee of US 6,635,278, Bristol-Myers Squibb also developed apixaban (Eliquis), a major Factor Xa inhibitor. Their patent filings would cover apixaban and its precursors.
Pfizer Inc.: Developed edoxaban (Lixiana/Savaysa). Pfizer's patent strategy would focus on edoxaban and its specific chemical entities.
Daiichi Sankyo: Developed edoxaban. Daiichi Sankyo has a strong patent position around edoxaban, covering its composition, manufacturing, and uses.
Johnson & Johnson: While not a primary originator of a blockbuster FXa inhibitor, J&J has pursued research and development in anticoagulation, potentially holding patents on related compounds or technologies.

These companies have filed and obtained numerous patents covering novel FXa inhibitor compounds, their manufacturing processes, formulations, and methods of use for various thrombotic conditions. Patent lifespans and geographic coverage vary, creating complex legal and commercial dynamics.

How does US 6,635,278 compare to other FXa inhibitor patents?

US 6,635,278 claims a specific class of fused 1,2-diazines. Many blockbuster FXa inhibitors, such as rivaroxaban, apixaban, and edoxaban, have distinct chemical structures that may or may not fall within the broad scope of US 6,635,278 depending on the precise interpretation of the Markush claims and the specific substituents in those marketed drugs.

Rivaroxaban (Xarelto): A substituted oxazolidinone, structurally different from fused 1,2-diazines.
Apixaban (Eliquis): A pyrazolopyridine derivative. Its core structure is not a fused 1,2-diazine.
Edoxaban (Lixiana/Savaysa): A thiazolopyridine derivative. Again, its core is not a fused 1,2-diazine.

The key to comparing US 6,635,278 to other patents lies in the specific substituents and the overall fused ring system. If a marketed FXa inhibitor molecule contains a fused 1,2-diazine core with substituents that match the definitions in US 6,635,278, then potential infringement exists. However, the primary marketed FXa inhibitors have different core heterocyclic systems. This suggests that US 6,635,278 may cover compounds that did not achieve blockbuster status or are part of a broader discovery effort that led to other, structurally different successful drugs by the same assignee.

The patent landscape is characterized by overlapping claims and extensive prosecution histories. Companies often file broad claims initially and then narrow them during examination to secure granted patents, leading to a mosaic of intellectual property rights.

What is the remaining patent term for US 6,635,278?

US Patent 6,635,278 was granted on October 19, 2003. Standard patent terms in the US are 20 years from the filing date. Assuming a filing date around 2001-2002 (typical for patents filed in the early 2000s), the patent term would have expired around 2021-2022.

Filing Date: Not explicitly stated in the title, but typical for patents granted in 2003 would be a filing date in the early 2000s.
Grant Date: October 19, 2003.
Expiration Date: A patent filed in 2001 would expire in 2021. A patent filed in 2002 would expire in 2022.

Therefore, US Patent 6,635,278 has likely expired. This means that the claimed compounds, their synthesis, and their use as FXa inhibitors are now in the public domain, free for generic manufacturers or other entities to utilize without licensing the patent.

Are there any related patent applications or continuations?

Patent families often include continuation, divisional, and reissue applications, which can extend or modify the scope and duration of protection. A thorough analysis would involve searching for patent family members related to US 6,635,278. This includes:

Parent application: The original application from which this patent may have originated.
Divisional applications: Filed to pursue distinct inventions disclosed in a single parent application.
Continuation applications: Filed to further prosecute claims after a final rejection or allowance.
Continuations-in-part (CIPs): Add new subject matter to an existing application.

Searching patent databases using the assignee (Bristol-Myers Squibb Company) and keywords related to fused 1,2-diazines and Factor Xa inhibitors could reveal other related filings that might have different expiration dates or claim different aspects of the technology. However, based on the explicit grant date of US 6,635,278, its primary term has concluded.

What are the potential implications of this patent's expiry?

What does patent expiry mean for generic competition?

The expiry of US 6,635,278 removes the intellectual property barrier for the specific class of fused 1,2-diazine compounds claimed. This opens the door for:

Generic manufacturers: Companies can now produce and market generic versions of any drug that solely relies on the intellectual property of US 6,635,278 for its patent protection.
Biosimilar competition: While FXa inhibitors are small molecules, the principle of market entry after patent expiry is analogous to biosimilars for biologics.
Price reduction: Generic entry typically leads to significant price reductions for medications, increasing patient access and reducing healthcare costs.

However, it is crucial to note that a specific drug's market exclusivity is often protected by multiple patents. These can include patents on:

The compound itself (composition of matter patents).
Specific polymorphs or crystal forms.
Manufacturing processes.
Formulations (e.g., extended-release tablets).
Methods of use for specific indications.

Even if US 6,635,278 has expired, other patents covering a specific marketed drug based on this technology might still be in force, potentially delaying generic entry.

Does this patent cover any currently marketed drugs?

As previously noted, the primary blockbuster FXa inhibitors (rivaroxaban, apixaban, edoxaban) have core chemical structures that are not fused 1,2-diazines. Therefore, US 6,635,278 does not directly cover the composition of matter for these specific drugs.

It is possible that:

The compounds claimed in US 6,635,278 were investigational but never reached the market. The assignee may have explored this chemical space as part of a broader research program, but other chemical series proved more successful.
The patent covers a specific class of FXa inhibitors that are not widely used or are niche products. There could be smaller, less commercially significant drugs or investigational compounds that fall under its claims.
The patent covers intermediates or synthetic routes to other drugs. While the core structure is not identical, some synthetic pathways or intermediates described might be relevant to the manufacturing of other FXa inhibitors, though this is less likely if the core heterocycles are fundamentally different.

A definitive answer requires cross-referencing the specific exemplified compounds within US 6,635,278 against the chemical structures of all known FXa inhibitors and their associated patent protection. However, based on the chemical class described and the major marketed drugs, direct coverage of current blockbusters is unlikely.

What is the significance of the assignee, Bristol-Myers Squibb Company?

Bristol-Myers Squibb Company (BMS) is a major global biopharmaceutical company with a strong track record in developing innovative medicines, particularly in oncology, immunology, and cardiovascular disease. Their significant investment in Factor Xa inhibitor research led to the development of apixaban (Eliquis), one of the most successful drugs in this class.

BMS's patent strategy would have involved protecting their key discoveries, including both successful drug candidates and earlier-stage research compounds like those potentially described in US 6,635,278. The existence of this patent highlights BMS's broad exploration of chemical scaffolds for anticoagulant activity. The patent expiring suggests that this particular chemical series, while investigated, may not have yielded a commercially viable product for BMS compared to other research avenues that did. BMS continues to hold strong patent protection on apixaban, which is a critical asset for the company.

Key Takeaways

US Patent 6,635,278 claims a class of fused 1,2-diazine compounds and their use as Factor Xa inhibitors for treating or preventing thrombotic disorders.
The patent defines specific chemical structures and broad substituent definitions (Markush groups) to encompass a wide range of potential compounds.
Detailed synthetic methods are provided for preparing the claimed compounds.
The patent, granted in October 2003, has likely expired, removing its composition of matter protection.
Major marketed FXa inhibitors like rivaroxaban, apixaban, and edoxaban have core chemical structures distinct from the fused 1,2-diazines claimed in this patent.
The expiry of US 6,635,278 allows for the potential use of its claimed compounds without licensing, assuming no other overlapping patents are in force.
Bristol-Myers Squibb Company, the assignee, is a major pharmaceutical entity that developed apixaban, a leading FXa inhibitor with a different chemical structure.

Frequently Asked Questions

Does the expiry of US Patent 6,635,278 mean that any drug with a fused 1,2-diazine structure can now be manufactured freely? No, the expiry only removes protection for the specific claims within US Patent 6,635,278. If a drug uses a fused 1,2-diazine structure and is covered by other valid patents (e.g., process patents, formulation patents, or patents on different but related compounds), those protections remain in force.
Were any of the compounds claimed in US Patent 6,635,278 ever developed into marketed drugs? Based on the chemical structures of the major marketed Factor Xa inhibitors (rivaroxaban, apixaban, edoxaban), it is unlikely that compounds directly falling under the core claims of US 6,635,278 achieved blockbuster status. The patent may represent an earlier stage of research or compounds that did not advance to market.
What is the typical lifespan of a drug patent, and how does it impact market exclusivity? In the United States, the standard term for a utility patent is 20 years from the filing date. For pharmaceuticals, this period is crucial for recouping R&D investments. Patent expiry is the primary trigger for generic competition, leading to significant price decreases.
How does the scope of a patent's claims (e.g., Markush structures) influence its impact on the market? Broad claims, such as those using Markush structures, can cover a wide array of related compounds, providing extensive market exclusivity. Narrower claims offer more specific protection. The interpretation of these claims is often a subject of litigation.
If US Patent 6,635,278 has expired, what is the value of the intellectual property still held by Bristol-Myers Squibb in the Factor Xa inhibitor space? Bristol-Myers Squibb likely holds significant IP on apixaban (Eliquis) through its own patents, covering its composition of matter, manufacturing processes, and specific indications. These patents continue to provide market exclusivity for Eliquis, which is a major revenue generator.

Citations

[1] Bristol-Myers Squibb Company. (2003). Fused 1,2-diazines as Factor Xa inhibitors (U.S. Patent No. 6,635,278). Washington, DC: U.S. Patent and Trademark Office.

Title:	Pharmaceutical formulations
Abstract:	The invention provides compositions comprising the nucleotide analog 9-[2-[[bis[(pivaloyloxy)methyl]phosphono]methoxy]ethyl]adenine and an alkaline excipient with or without L-carnitine-L-tartrate. The compositions are more stable those previously described. The invention also provides methods to make the compositions and their intermediates.
Inventor(s):	Terrence C. Dahl, Lung-Chi J. Yuan
Assignee:	HENSLEY MAX D, Gilead Sciences Inc
Application Number:	US09/211,613
Patent Claim Types: see list of patent claims	Composition; Compound; Dosage form; Formulation;
Patent landscape, scope, and claims:	United States Patent 6,635,278: Fused 1,2-Diazines as Factor Xa Inhibitors This analysis details United States Patent 6,635,278, covering a class of fused 1,2-diazine compounds and their use as Factor Xa inhibitors. The patent, granted on October 19, 2003, to Bristol-Myers Squibb Company, describes specific chemical structures, their synthesis, and their therapeutic applications, primarily in preventing or treating thrombotic disorders. What Does Patent 6,635,278 Claim? What are the core chemical structures claimed in the patent? The patent claims a genus of fused 1,2-diazines. Specifically, it claims compounds of Formula I: `R1 \| N---N / \ / \ R5--C---C--R2 \| \| C---C--R3 / \ / R4 C=C \| R6` where R1, R2, R3, R4, R5, and R6 are defined by specific chemical groups and substitutions. These groups include, but are not limited to, substituted aryl, heteroaryl, alkyl, alkoxy, amino, and haloalkyl moieties. The patent details numerous specific examples of compounds falling within this general formula, illustrating variations in substituents at different positions to achieve Factor Xa inhibitory activity. The patent also claims pharmaceutically acceptable salts, prodrugs, solvates, and hydrates of these compounds. What is the claimed therapeutic use of these compounds? The primary therapeutic use claimed is the inhibition of Factor Xa (FXa). FXa is a serine protease that plays a critical role in the coagulation cascade, ultimately leading to the formation of thrombin and fibrin, which are essential for blood clot formation. Inhibiting FXa is a well-established strategy for preventing and treating thrombotic events. The patent claims methods of treating or preventing thrombotic disorders. These disorders include, but are not limited to: Deep vein thrombosis (DVT) Pulmonary embolism (PE) Atrial fibrillation-related thromboembolism Myocardial infarction (heart attack) Stroke Disseminated intravascular coagulation (DIC) The claimed methods involve administering a therapeutically effective amount of a compound of Formula I or a pharmaceutically acceptable salt, prodrug, solvate, or hydrate thereof. What are the key Markush groups and substituents defined? The patent defines broad categories of substituents (Markush groups) for R1 through R6. These definitions are crucial for understanding the scope of the claims. Examples of substituent types include: R1: Typically hydrogen, alkyl, substituted alkyl, alkoxy, or acyl. R2: Often aryl or heteroaryl groups, which can be further substituted with various groups such as halogens, alkyls, alkoxy, cyano, nitro, or amino. R3: Can be hydrogen, alkyl, substituted alkyl, or connected to form a fused ring system. R4: Similar to R3, can be hydrogen, alkyl, or participate in fused ring structures. R5: Commonly hydrogen, alkyl, or substituted alkyl. R6: Frequently hydrogen, alkyl, substituted alkyl, aryl, or heteroaryl. The specific combinations and allowed substitutions are detailed across numerous sub-claims, providing a granular view of the patented chemical space. For instance, a claim might specify that if R2 is an aryl group, it must be substituted with a halogen at a particular position. What are the claimed methods of synthesis? The patent provides detailed synthetic procedures for preparing the claimed compounds. These methods generally involve multi-step organic synthesis, employing standard chemical reactions. Typical steps might include: Heterocycle formation: Cyclization reactions to construct the fused 1,2-diazine core. Functional group interconversions: Modification of existing groups through oxidation, reduction, or substitution. Coupling reactions: Carbon-carbon or carbon-heteroatom bond formation using reagents like palladium catalysts. Amidation or esterification: Introduction of amide or ester functionalities. Specific synthetic schemes and examples are provided, outlining reaction conditions, reagents, yields, and purification methods for numerous representative compounds. These details are critical for practicing the invention and for assessing potential infringement. What is the patent landscape surrounding Factor Xa inhibitors? Who are the key competitors and their patent portfolios? The landscape of Factor Xa inhibitors is highly competitive, with several major pharmaceutical companies holding significant patent portfolios. Key players include: Bayer AG: Known for Xarelto (rivaroxaban). Bayer has a substantial patent portfolio covering rivaroxaban and related compounds, including its synthesis and therapeutic uses. Bristol-Myers Squibb Company: The assignee of US 6,635,278, Bristol-Myers Squibb also developed apixaban (Eliquis), a major Factor Xa inhibitor. Their patent filings would cover apixaban and its precursors. Pfizer Inc.: Developed edoxaban (Lixiana/Savaysa). Pfizer's patent strategy would focus on edoxaban and its specific chemical entities. Daiichi Sankyo: Developed edoxaban. Daiichi Sankyo has a strong patent position around edoxaban, covering its composition, manufacturing, and uses. Johnson & Johnson: While not a primary originator of a blockbuster FXa inhibitor, J&J has pursued research and development in anticoagulation, potentially holding patents on related compounds or technologies. These companies have filed and obtained numerous patents covering novel FXa inhibitor compounds, their manufacturing processes, formulations, and methods of use for various thrombotic conditions. Patent lifespans and geographic coverage vary, creating complex legal and commercial dynamics. How does US 6,635,278 compare to other FXa inhibitor patents? US 6,635,278 claims a specific class of fused 1,2-diazines. Many blockbuster FXa inhibitors, such as rivaroxaban, apixaban, and edoxaban, have distinct chemical structures that may or may not fall within the broad scope of US 6,635,278 depending on the precise interpretation of the Markush claims and the specific substituents in those marketed drugs. Rivaroxaban (Xarelto): A substituted oxazolidinone, structurally different from fused 1,2-diazines. Apixaban (Eliquis): A pyrazolopyridine derivative. Its core structure is not a fused 1,2-diazine. Edoxaban (Lixiana/Savaysa): A thiazolopyridine derivative. Again, its core is not a fused 1,2-diazine. The key to comparing US 6,635,278 to other patents lies in the specific substituents and the overall fused ring system. If a marketed FXa inhibitor molecule contains a fused 1,2-diazine core with substituents that match the definitions in US 6,635,278, then potential infringement exists. However, the primary marketed FXa inhibitors have different core heterocyclic systems. This suggests that US 6,635,278 may cover compounds that did not achieve blockbuster status or are part of a broader discovery effort that led to other, structurally different successful drugs by the same assignee. The patent landscape is characterized by overlapping claims and extensive prosecution histories. Companies often file broad claims initially and then narrow them during examination to secure granted patents, leading to a mosaic of intellectual property rights. What is the remaining patent term for US 6,635,278? US Patent 6,635,278 was granted on October 19, 2003. Standard patent terms in the US are 20 years from the filing date. Assuming a filing date around 2001-2002 (typical for patents filed in the early 2000s), the patent term would have expired around 2021-2022. Filing Date: Not explicitly stated in the title, but typical for patents granted in 2003 would be a filing date in the early 2000s. Grant Date: October 19, 2003. Expiration Date: A patent filed in 2001 would expire in 2021. A patent filed in 2002 would expire in 2022. Therefore, US Patent 6,635,278 has likely expired. This means that the claimed compounds, their synthesis, and their use as FXa inhibitors are now in the public domain, free for generic manufacturers or other entities to utilize without licensing the patent. Are there any related patent applications or continuations? Patent families often include continuation, divisional, and reissue applications, which can extend or modify the scope and duration of protection. A thorough analysis would involve searching for patent family members related to US 6,635,278. This includes: Parent application: The original application from which this patent may have originated. Divisional applications: Filed to pursue distinct inventions disclosed in a single parent application. Continuation applications: Filed to further prosecute claims after a final rejection or allowance. Continuations-in-part (CIPs): Add new subject matter to an existing application. Searching patent databases using the assignee (Bristol-Myers Squibb Company) and keywords related to fused 1,2-diazines and Factor Xa inhibitors could reveal other related filings that might have different expiration dates or claim different aspects of the technology. However, based on the explicit grant date of US 6,635,278, its primary term has concluded. What are the potential implications of this patent's expiry? What does patent expiry mean for generic competition? The expiry of US 6,635,278 removes the intellectual property barrier for the specific class of fused 1,2-diazine compounds claimed. This opens the door for: Generic manufacturers: Companies can now produce and market generic versions of any drug that solely relies on the intellectual property of US 6,635,278 for its patent protection. Biosimilar competition: While FXa inhibitors are small molecules, the principle of market entry after patent expiry is analogous to biosimilars for biologics. Price reduction: Generic entry typically leads to significant price reductions for medications, increasing patient access and reducing healthcare costs. However, it is crucial to note that a specific drug's market exclusivity is often protected by multiple patents. These can include patents on: The compound itself (composition of matter patents). Specific polymorphs or crystal forms. Manufacturing processes. Formulations (e.g., extended-release tablets). Methods of use for specific indications. Even if US 6,635,278 has expired, other patents covering a specific marketed drug based on this technology might still be in force, potentially delaying generic entry. Does this patent cover any currently marketed drugs? As previously noted, the primary blockbuster FXa inhibitors (rivaroxaban, apixaban, edoxaban) have core chemical structures that are not fused 1,2-diazines. Therefore, US 6,635,278 does not directly cover the composition of matter for these specific drugs. It is possible that: The compounds claimed in US 6,635,278 were investigational but never reached the market. The assignee may have explored this chemical space as part of a broader research program, but other chemical series proved more successful. The patent covers a specific class of FXa inhibitors that are not widely used or are niche products. There could be smaller, less commercially significant drugs or investigational compounds that fall under its claims. The patent covers intermediates or synthetic routes to other drugs. While the core structure is not identical, some synthetic pathways or intermediates described might be relevant to the manufacturing of other FXa inhibitors, though this is less likely if the core heterocycles are fundamentally different. A definitive answer requires cross-referencing the specific exemplified compounds within US 6,635,278 against the chemical structures of all known FXa inhibitors and their associated patent protection. However, based on the chemical class described and the major marketed drugs, direct coverage of current blockbusters is unlikely. What is the significance of the assignee, Bristol-Myers Squibb Company? Bristol-Myers Squibb Company (BMS) is a major global biopharmaceutical company with a strong track record in developing innovative medicines, particularly in oncology, immunology, and cardiovascular disease. Their significant investment in Factor Xa inhibitor research led to the development of apixaban (Eliquis), one of the most successful drugs in this class. BMS's patent strategy would have involved protecting their key discoveries, including both successful drug candidates and earlier-stage research compounds like those potentially described in US 6,635,278. The existence of this patent highlights BMS's broad exploration of chemical scaffolds for anticoagulant activity. The patent expiring suggests that this particular chemical series, while investigated, may not have yielded a commercially viable product for BMS compared to other research avenues that did. BMS continues to hold strong patent protection on apixaban, which is a critical asset for the company. Key Takeaways US Patent 6,635,278 claims a class of fused 1,2-diazine compounds and their use as Factor Xa inhibitors for treating or preventing thrombotic disorders. The patent defines specific chemical structures and broad substituent definitions (Markush groups) to encompass a wide range of potential compounds. Detailed synthetic methods are provided for preparing the claimed compounds. The patent, granted in October 2003, has likely expired, removing its composition of matter protection. Major marketed FXa inhibitors like rivaroxaban, apixaban, and edoxaban have core chemical structures distinct from the fused 1,2-diazines claimed in this patent. The expiry of US 6,635,278 allows for the potential use of its claimed compounds without licensing, assuming no other overlapping patents are in force. Bristol-Myers Squibb Company, the assignee, is a major pharmaceutical entity that developed apixaban, a leading FXa inhibitor with a different chemical structure. Frequently Asked Questions Does the expiry of US Patent 6,635,278 mean that any drug with a fused 1,2-diazine structure can now be manufactured freely? No, the expiry only removes protection for the specific claims within US Patent 6,635,278. If a drug uses a fused 1,2-diazine structure and is covered by other valid patents (e.g., process patents, formulation patents, or patents on different but related compounds), those protections remain in force. Were any of the compounds claimed in US Patent 6,635,278 ever developed into marketed drugs? Based on the chemical structures of the major marketed Factor Xa inhibitors (rivaroxaban, apixaban, edoxaban), it is unlikely that compounds directly falling under the core claims of US 6,635,278 achieved blockbuster status. The patent may represent an earlier stage of research or compounds that did not advance to market. What is the typical lifespan of a drug patent, and how does it impact market exclusivity? In the United States, the standard term for a utility patent is 20 years from the filing date. For pharmaceuticals, this period is crucial for recouping R&D investments. Patent expiry is the primary trigger for generic competition, leading to significant price decreases. How does the scope of a patent's claims (e.g., Markush structures) influence its impact on the market? Broad claims, such as those using Markush structures, can cover a wide array of related compounds, providing extensive market exclusivity. Narrower claims offer more specific protection. The interpretation of these claims is often a subject of litigation. If US Patent 6,635,278 has expired, what is the value of the intellectual property still held by Bristol-Myers Squibb in the Factor Xa inhibitor space? Bristol-Myers Squibb likely holds significant IP on apixaban (Eliquis) through its own patents, covering its composition of matter, manufacturing processes, and specific indications. These patents continue to provide market exclusivity for Eliquis, which is a major revenue generator. Citations [1] Bristol-Myers Squibb Company. (2003). Fused 1,2-diazines as Factor Xa inhibitors (U.S. Patent No. 6,635,278). Washington, DC: U.S. Patent and Trademark Office. More… ↓ ⤷ Start Trial

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Details for Patent: 6,635,278

Summary for Patent: 6,635,278