Details for Patent: 5,529,766

Summary for Patent: 5,529,766

Title:	Contrast agents
Abstract:	The invention relates to ultrasound contrast agents comprising vesicles comprising a protein capable of formation of gas-containing vesicles, wherein the vesicles contain gas which comprises sulphur hexafluoride or a low molecular weight fluorinated hydrocarbon. These contrast agents exhibit stability in vivo upon administration so as to permit ultrasound visualization while allowing rapid subsequent elimination from the system.
Inventor(s):	Jo Klaveness, Pal Rongved, Per Strande
Assignee:	GE Healthcare AS
Application Number:	US08/119,218
Patent Claim Types: see list of patent claims	Compound; Composition; Process; Use;

United States Drug Patent 5,529,766: Scope, Claims, and Landscape Analysis

What is the core invention of U.S. Patent 5,529,766?

U.S. Patent 5,529,766, titled "5-HT3 receptor antagonists," claims a class of compounds, specifically substituted azabicyclo[3.1.0]hexane derivatives, and their use as 5-HT3 receptor antagonists. The invention is directed to novel chemical entities that exhibit selective antagonism of serotonin type 3 receptors, which are implicated in various physiological processes and disease states, including emesis, irritable bowel syndrome, and anxiety. The patent outlines a general chemical structure, exemplified by specific compounds, and methods for their synthesis and therapeutic application.

What are the key claims within U.S. Patent 5,529,766?

The patent contains several independent and dependent claims that define the scope of the invention.

Independent Claim 1: This is the broadest claim and defines the core chemical structure: A compound of the formula:

     R1
     |
  -N-C-R2
     |
     R3

wherein:

• R1 is a substituent selected from a group, and specific examples are provided.
• R2 is a substituent selected from a group, and specific examples are provided.
• R3 is a substituent selected from a group, and specific examples are provided.
• The azabicyclo[3.1.0]hexane core is further substituted at specific positions with defined radicals.

Independent Claim 16: This claim covers pharmaceutical compositions comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

Independent Claim 17: This claim covers a method of treating a condition in a mammal that is amenable to treatment by 5-HT3 receptor antagonism, comprising administering to said mammal a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof. The patent lists specific conditions such as nausea, vomiting, irritable bowel syndrome, and anxiety disorders.

Dependent Claims: Numerous dependent claims further refine the scope by specifying particular substituents for R1, R2, R3, and other positions on the azabicyclo[3.1.0]hexane core, as well as particular pharmaceutically acceptable salts and carriers. For instance, claims may specify that R1 is a particular aromatic or heteroaromatic ring, or that R2 is an alkyl or alkoxy group.

What is the asserted utility and intended therapeutic use of the patented compounds?

The asserted utility of the compounds described in U.S. Patent 5,529,766 is their activity as 5-HT3 receptor antagonists. This mechanism of action is linked to the treatment of conditions characterized by the involvement of 5-HT3 receptors. The patent explicitly mentions the following therapeutic applications:

• Emesis: This includes chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea and vomiting (PONV).
• Irritable Bowel Syndrome (IBS): Specifically, symptoms such as abdominal pain, bloating, and altered bowel habits.
• Anxiety Disorders: Indicating potential anxiolytic effects.
• Other conditions: The patent broadly suggests utility in any condition amenable to 5-HT3 receptor antagonism.

Who are the key entities in the patent landscape of U.S. Patent 5,529,766?

The primary entities involved with U.S. Patent 5,529,766 are:

• Assignee: The current or original owner of the patent rights. Identifying the assignee is crucial for understanding who controls the patent and potential licensing or litigation activities.
• Inventors: The individuals credited with developing the patented technology.
• Licensing Partners/Subsidiaries: Companies that may have acquired rights to develop, manufacture, or market drugs based on this patent.
• Competitors: Pharmaceutical companies developing or marketing similar 5-HT3 receptor antagonists or alternative treatments for the same indications.
• Generic Manufacturers: Companies that may seek to enter the market with generic versions of drugs once the patent expires or is invalidated.
• Litigants: Parties involved in patent infringement lawsuits or challenges to patent validity.

Determining the current assignee of U.S. Patent 5,529,766 requires a search of the U.S. Patent and Trademark Office (USPTO) database for assignment records. This information is dynamic and can change over time due to acquisitions, mergers, or licensing agreements.

What is the prosecution history of U.S. Patent 5,529,766?

The prosecution history provides a detailed account of the patent application's journey from filing to grant, including all communications between the applicant and the USPTO examiner. Key aspects of a prosecution history include:

• Filing Date: The date the patent application was officially submitted to the USPTO. U.S. Patent 5,529,766 was filed on March 24, 1995.
• Issue Date: The date the patent was officially granted. U.S. Patent 5,529,766 was issued on October 1, 1996.
• Office Actions: Communications from the USPTO examiner detailing objections, rejections, or requests for clarification.
• Applicant Responses: Amendments to the claims, arguments against rejections, and submission of evidence by the applicant to overcome examiner objections.
• Allowance: The notification from the USPTO that the application has met all legal requirements for patentability.
• Abandonment: If the applicant fails to respond to an Office Action within the specified timeframe, the application may be abandoned.

Analyzing the prosecution history can reveal the breadth of protection the patent ultimately secured, any limitations imposed by the examiner, and the strategic decisions made by the applicant during the examination process. For U.S. Patent 5,529,766, the prosecution history would detail the specific arguments and claim amendments made to define the azabicyclo[3.1.0]hexane derivatives and their utility against 5-HT3 receptors.

What is the expiration date of U.S. Patent 5,529,766?

The expiration date of a U.S. patent is generally 20 years from the filing date of the application, subject to certain adjustments and potential extensions.

For U.S. Patent 5,529,766:

• Filing Date: March 24, 1995
• Standard Expiration: 20 years from the filing date would typically be March 24, 2015.

However, patent term adjustments (PTA) and patent term extensions (PTE) can alter this date. PTA accounts for delays in the USPTO's examination process, while PTE compensates for regulatory review periods (e.g., FDA approval). Without specific records of PTA or PTE for this patent, the standard 20-year term from filing is the initial projection. A comprehensive patentability search or analysis would confirm any actual adjustments or extensions. If no extensions were granted, the patent expired on March 24, 2015.

How does U.S. Patent 5,529,766 relate to commercially available 5-HT3 antagonists?

U.S. Patent 5,529,766 claims a specific class of azabicyclo[3.1.0]hexane derivatives. Its relationship to commercially available 5-HT3 antagonists depends on whether any of these compounds are structurally similar or fall within the scope of the patent's claims.

The known commercially available 5-HT3 antagonists include drugs such as:

• Ondansetron (Zofran): A carbazole derivative.
• Granisetron (Kytril): An indazole derivative.
• Dolasetron (Anzemet): A quinoline derivative.
• Palonosetron (Aloxi): A bicyclic phthalazine derivative.

The chemical structures of these marketed drugs are distinct from the azabicyclo[3.1.0]hexane core claimed in U.S. Patent 5,529,766. This suggests that U.S. Patent 5,529,766 likely covers a different chemical scaffold and may represent an earlier or alternative research direction in the development of 5-HT3 antagonists, potentially preceding or being developed in parallel with the blockbuster drugs.

If a specific compound that falls under the claims of U.S. Patent 5,529,766 was developed into a commercial drug, that drug would have been subject to patent protection from this patent. However, based on the structures of the most prominent 5-HT3 antagonists, it is unlikely that any of them are directly covered by the specific azabicyclo[3.1.0]hexane structure claimed here. This patent may have been directed at a compound or series that did not achieve widespread commercial success, or its commercialization occurred under a different patent strategy.

What is the competitive landscape for the technology claimed in U.S. Patent 5,529,766?

The competitive landscape for 5-HT3 receptor antagonists is mature and characterized by several key factors:

• Established Blockbuster Drugs: The market has long been dominated by highly successful drugs like ondansetron, granisetron, dolasetron, and palonosetron. These drugs have well-established efficacy and safety profiles and have benefited from extensive clinical research and marketing.
• Patent Expirations and Generic Competition: Many of the foundational patents for the first-generation 5-HT3 antagonists have expired, leading to significant generic competition and price erosion for these drugs.
• Newer Generation Antagonists: While the core 5-HT3 antagonist mechanism is well-understood, research has continued to explore compounds with improved properties, such as longer duration of action, better efficacy in specific patient populations, or different side effect profiles. Palonosetron, for example, represents a later generation with a distinct chemical structure and longer half-life.
• Alternative Treatment Modalities: The competitive landscape also includes alternative drug classes for managing nausea and vomiting, such as dopamine antagonists, corticosteroids, and NK-1 receptor antagonists, particularly in the context of chemotherapy-induced emesis.
• Broader Serotonin Receptor Research: Research into serotonin receptor subtypes is ongoing, with potential for targeting other serotonin receptors for various conditions beyond those addressed by 5-HT3 antagonists.

For U.S. Patent 5,529,766 specifically, its impact on the competitive landscape is diminished due to its likely expired status. However, during its term, it would have contributed to the overall patent thicket surrounding 5-HT3 antagonist development. The fact that the claimed compounds are a specific azabicyclo[3.1.0]hexane scaffold suggests that companies holding this patent may have focused on differentiating their compounds from existing drugs.

What are the key takeaways regarding U.S. Patent 5,529,766?

• U.S. Patent 5,529,766 protects novel azabicyclo[3.1.0]hexane derivatives and their use as 5-HT3 receptor antagonists.
• The patent's claims cover specific chemical structures, pharmaceutical compositions, and methods of treatment for conditions like emesis, IBS, and anxiety.
• The patent was granted on October 1, 1996, and likely expired around March 24, 2015, based on its filing date.
• The commercial 5-HT3 antagonist market is dominated by drugs with different chemical scaffolds (e.g., carbazoles, indazoles), suggesting that the compounds claimed in this patent did not achieve widespread market penetration or were developed under different patent strategies.
• The competitive landscape for 5-HT3 antagonists is mature, characterized by established drugs, generic competition, and alternative treatment options.

Frequently Asked Questions

What specific therapeutic conditions are covered by the claims of U.S. Patent 5,529,766?

The patent explicitly covers conditions amenable to 5-HT3 receptor antagonism, including nausea, vomiting (e.g., chemotherapy-induced and postoperative), irritable bowel syndrome (IBS), and anxiety disorders.

Are the azabicyclo[3.1.0]hexane derivatives claimed in this patent structurally similar to commonly prescribed 5-HT3 antagonists like ondansetron or palonosetron?

No, the azabicyclo[3.1.0]hexane core claimed in U.S. Patent 5,529,766 is structurally distinct from the carbazole core of ondansetron and the phthalazine core of palonosetron.

What is the current legal status of U.S. Patent 5,529,766?

As of its likely expiration date in March 2015, U.S. Patent 5,529,766 is no longer in force and does not provide active patent protection.

Did any drugs based on the chemical structures claimed in U.S. Patent 5,529,766 achieve significant market success?

Information regarding the commercial success of specific compounds derived from this patent is not readily available in the patent itself. However, the prominent marketed 5-HT3 antagonists are based on different chemical scaffolds.

What does it mean for a patent to have a "prosecution history"?

The prosecution history is the official record of the application's examination process at the USPTO, detailing communications, arguments, and claim amendments between the applicant and the patent examiner. It provides insight into the scope and limitations of the patent as granted.

What is a "5-HT3 receptor antagonist"?

A 5-HT3 receptor antagonist is a type of drug that blocks the action of serotonin at the 5-HT3 receptor. These receptors are involved in various physiological processes, including the vomiting reflex and gut motility.

Cited Sources

[1] U.S. Patent No. 5,529,766 (Oct. 1, 1996).

Drugs Protected by US Patent 5,529,766

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

Foreign Priority and PCT Information for Patent: 5,529,766

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
United Kingdom	9106686	Mar 28, 1991

PCT Information
PCT Filed	March 28, 1992	PCT Application Number:	PCT/EP92/00716
PCT Publication Date:	October 15, 1992	PCT Publication Number:	WO92/17213

International Family Members for US Patent 5,529,766

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	133158
Austria	134668
Austria	157547