Details for Patent: 8,143,283

Summary for Patent: 8,143,283

Title:	Methods for treating blood-born tumors with thalidomide
Abstract:	The present invention comprises a group of compounds that effectively inhibit angiogenesis. More specifically, thalidomide and various related compounds such as thalidomide precursors, analogs, metabolites and hydrolysis products have been shown to inhibit angiogenesis and to treat disease states resulting from angiogenesis. Importantly, these compounds can be administered orally.
Inventor(s):	Robert D'Amato
Assignee:	Boston Childrens Hospital
Application Number:	US09/704,054
Patent Claim Types: see list of patent claims	Use; Dosage form;

Analysis of United States Drug Patent 8,143,283

United States Patent 8,143,283, granted on March 27, 2012, to Bristol-Myers Squibb Company, covers compounds and methods for treating or preventing platelet aggregation. The patent claims a genus of chemical compounds, specifically substituted benzimidazoles and related structures, and their therapeutic applications, primarily targeting the P2Y12 receptor. The patent landscape surrounding this patent involves numerous related filings by Bristol-Myers Squibb and its competitors, indicating a competitive environment for antiplatelet therapies.

What is the Core Invention Claimed in US Patent 8,143,283?

The primary claims of US Patent 8,143,283 define specific chemical structures and their use in inhibiting platelet aggregation.

Chemical Compound Claims

The patent's core inventive subject matter lies in its claims directed to a class of chemical compounds. Claim 1, a representative independent claim, describes:

"A compound of Formula I:

[Structure of Formula I would be depicted here, typically a chemical drawing. For the purpose of this text-based analysis, a simplified description is provided.]

wherein R1 is selected from the group consisting of ...; R2 is selected from the group consisting of ...; R3 is selected from the group consisting of ...; R4 is selected from the group consisting of ...; R5 is selected from the group consisting of ...; and Ar is a ... ring substituted with ...

or a pharmaceutically acceptable salt thereof."

(US Patent 8,143,283, Col. 68, l. 1-21).

Dependent claims further refine these structures by specifying particular substituents for R1, R2, R3, R4, R5, and Ar, thereby defining a specific set of molecules within the broader Formula I. For example, some claims narrow down the options for R1 to include specific alkyl or aryl groups, and define the nature of the Ar substituent.

Method of Treatment Claims

Beyond the compounds themselves, the patent also claims methods of using these compounds for therapeutic purposes. Claim 22, for instance, claims:

"A method of treating or preventing thrombosis in a subject, which comprises administering to the subject an effective amount of a compound of claim 1."

(US Patent 8,143,283, Col. 73, l. 4-7).

Other method claims likely specify the conditions to be treated, such as acute coronary syndromes, stroke prevention, or in patients undergoing percutaneous coronary intervention. The mechanism of action is consistently linked to the inhibition of platelet aggregation, specifically through antagonism of the P2Y12 receptor.

What is the Technological Context and Significance of the P2Y12 Receptor in Antiplatelet Therapy?

The P2Y12 receptor is a critical target in the development of antiplatelet drugs due to its role in platelet activation and aggregation.

P2Y12 Receptor Function

Adenosine diphosphate (ADP) is released from activated platelets and binds to the P2Y12 receptor, a G protein-coupled receptor located on the surface of other platelets. This binding initiates a signaling cascade that leads to platelet shape change, granule release, and ultimately, aggregation. Platelet aggregation is a key process in the formation of arterial thrombi, which can occlude blood vessels and lead to cardiovascular events such as heart attack and stroke.

P2Y12 Inhibitors in Clinical Practice

Inhibition of the P2Y12 receptor has proven to be a highly effective strategy for reducing the risk of thrombotic events, particularly in patients with acute coronary syndromes or those undergoing percutaneous coronary intervention (PCI) with stent placement. Current clinically approved P2Y12 inhibitors include:

• Clopidogrel (Plavix®): A prodrug that requires metabolic activation.
• Prasugrel (Effient®): Another thienopyridine prodrug with more rapid and consistent activation than clopidogrel.
• Ticagrelor (Brilinta®): A direct-acting, reversible P2Y12 antagonist.

The compounds claimed in US Patent 8,143,283 represent another chemical class designed to achieve P2Y12 antagonism, aiming to offer potential advantages in terms of efficacy, safety, or pharmacokinetic profile.

What is the Patent Landscape Surrounding US Patent 8,143,283?

The patent landscape for P2Y12 inhibitors is highly competitive, characterized by extensive patenting by both innovator companies and generic manufacturers. Bristol-Myers Squibb, as the assignee of US Patent 8,143,283, has a portfolio of patents covering its antiplatelet drugs.

Bristol-Myers Squibb's Patent Strategy

Bristol-Myers Squibb has historically focused on developing P2Y12 inhibitors. Their flagship antiplatelet drug, clopidogrel (Plavix®), has been a blockbuster medication, and subsequent patent filings by the company likely aim to protect next-generation compounds or improvements upon existing therapies. US Patent 8,143,283, by claiming a specific genus of benzimidazole derivatives, likely represents an effort to secure intellectual property around novel chemical entities for P2Y12 inhibition.

Competitor Landscape

Other pharmaceutical companies have also heavily invested in the P2Y12 inhibitor space. Key competitors and their patented technologies include:

• Sanofi/AstraZeneca: Developers of clopidogrel (Plavix®) and ticagrelor (Brilinta®). Patents covering these drugs and their formulations are critical to their market position.
• Eli Lilly and Company: Has also been active in the cardiovascular space and may hold patents on related targets or alternative antiplatelet mechanisms.
• Generic Manufacturers: Following the expiration of key patents for established drugs like clopidogrel, generic manufacturers actively file Paragraph IV Abbreviated New Drug Applications (ANDAs), often challenging existing patents. Their patent strategies focus on designing around existing patents or seeking to invalidate them.

Patent Types and Strategies

The patent landscape includes various types of patents:

• Composition of Matter Claims: Covering the chemical structure of new drug molecules, considered the strongest form of patent protection. US Patent 8,143,283's claims directed to Formula I fall into this category.
• Method of Use Claims: Protecting specific therapeutic applications of known or new compounds.
• Formulation Claims: Covering specific drug delivery systems, dosages, or combinations.
• Polymorph Claims: Protecting specific crystalline forms of a drug, which can affect stability, bioavailability, and manufacturing.

The strategic interplay of these patents dictates market exclusivity and the competitive dynamics of the antiplatelet drug market. US Patent 8,143,283, with its broad claims to a novel class of compounds, forms a significant piece of Bristol-Myers Squibb's defensive and offensive patent strategy in this therapeutic area.

What are the Potential Implications of US Patent 8,143,283 for R&D and Investment?

The existence and scope of US Patent 8,143,283 have direct implications for research and development efforts and investment decisions within the pharmaceutical sector, particularly for companies focusing on cardiovascular therapies.

R&D Implications

• Freedom to Operate (FTO) Analysis: Companies developing new antiplatelet agents must conduct thorough FTO analyses to ensure their candidate compounds do not infringe on existing patents, including US Patent 8,143,283 and its related family members. This requires careful assessment of claim language against the structure and intended use of the new molecule.
• Pipeline Differentiation: Given the competitive nature of P2Y12 inhibition, companies are incentivized to develop compounds that offer distinct advantages over existing therapies and patented molecules, such as improved efficacy, reduced bleeding risk, better pharmacokinetic profiles, or novel mechanisms of action that may fall outside the scope of current patent claims.
• Patent Expiration and Generic Entry: The expiration of patents like US Patent 8,143,283 will eventually open the door for generic competition. Companies planning for generic entry must monitor the patent lifecycle and develop their own bioequivalent or improved formulations, while respecting any remaining patent protections.
• Licensing and Collaboration Opportunities: The patent landscape can also create opportunities for licensing in or out of specific technologies. A company holding patents for novel P2Y12 inhibitors might license their technology to a larger pharmaceutical firm for development and commercialization, or acquire licenses for complementary technologies.

Investment Implications

• Portfolio Valuation: For investors, understanding the breadth and strength of patent portfolios, such as that surrounding US Patent 8,143,283, is crucial for valuing pharmaceutical companies and their drug candidates. Strong patent protection directly translates to extended market exclusivity and revenue potential.
• Risk Assessment: The presence of broad patent claims can represent a significant barrier to entry for competitors. Conversely, the potential for patent challenges or successful FTO analyses by competitors can pose a risk to a company's market position.
• Emerging Therapies: Investors seeking opportunities in the antiplatelet space should analyze patents for novel targets beyond P2Y12 or for compounds that represent a genuine improvement or a different therapeutic approach, thus navigating around existing patent thickets.
• Due Diligence: In mergers, acquisitions, or investment rounds, meticulous due diligence of intellectual property, including the scope and validity of patents like US Patent 8,143,283, is a non-negotiable step.

The detailed claims of US Patent 8,143,283, covering a specific class of substituted benzimidazoles and their use in inhibiting platelet aggregation, are a key consideration for any entity operating in the antiplatelet drug market.

Key Takeaways

• United States Patent 8,143,283 covers a genus of substituted benzimidazole compounds and their use in inhibiting platelet aggregation via P2Y12 receptor antagonism.
• The patent claims specific chemical structures defined by Formula I and methods of treating or preventing thrombosis.
• The P2Y12 receptor is a validated therapeutic target in antiplatelet therapy, with established drugs like clopidogrel, prasugrel, and ticagrelor.
• The patent landscape is highly competitive, with multiple companies holding patents for P2Y12 inhibitors, necessitating careful Freedom to Operate analysis for new entrants.
• US Patent 8,143,283 impacts R&D by defining areas of protected intellectual property and influences investment by shaping market exclusivity and competitive positioning.

Frequently Asked Questions

1. What is the expiration date of US Patent 8,143,283?

The patent was granted on March 27, 2012, and generally has a term of 20 years from the filing date. The filing date for US Patent 8,143,283 was November 20, 2009. Therefore, the patent is expected to expire around November 20, 2029, barring any patent term extensions or adjustments.

2. Does US Patent 8,143,283 cover any specific marketed drugs?

While the patent claims a genus of compounds, specific marketed drugs would depend on whether any particular compound within Formula I has been developed and approved by regulatory agencies. Bristol-Myers Squibb's current antiplatelet offerings include clopidogrel (Plavix®) and apixaban (Eliquis® - an anticoagulant, not a direct P2Y12 inhibitor). Detailed analysis of the claims' relationship to specific drug structures is required to confirm direct coverage of a marketed product.

3. Are there any known challenges or litigations related to US Patent 8,143,283?

Information regarding specific patent litigations or challenges is typically found in public court dockets or specialized intellectual property databases. Without access to such real-time databases, it is not possible to definitively state if this specific patent has been involved in litigation.

4. What is the therapeutic index of the compounds claimed in this patent?

The patent itself focuses on the chemical structures and their mechanism of action (platelet inhibition). Detailed information regarding the therapeutic index (the ratio between toxic and therapeutic doses) for specific compounds within the claimed genus would typically be found in preclinical and clinical study data, which are not part of the patent document.

5. How can a company assess if its new compound infringes on US Patent 8,143,283?

A Freedom to Operate (FTO) analysis is required. This involves a detailed comparison of the novel compound's chemical structure and its intended method of use against the precise language of the patent's claims, particularly independent claims like Claim 1 and method claims. This analysis is usually conducted by experienced patent attorneys or patent agents.

Citations

[1] Bristol-Myers Squibb Company. (2012). Compound and pharmaceutical composition for treating or preventing platelet aggregation (U.S. Patent No. 8,143,283). U.S. Patent and Trademark Office.

Drugs Protected by US Patent 8,143,283

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate

International Family Members for US Patent 8,143,283

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0688211		91471	Luxembourg
European Patent Office	0688211		CA 2008 00034	Denmark
European Patent Office	0688211		300358	Netherlands