Details for Patent: 6,385,488

Summary for Patent: 6,385,488

Title:	Circuits for increasing the reliability of an iontophoretic system
Abstract:	Circuits are provided for increasing the reliability of an iontophoretic drug delivery system. Such circuits detect the failure of a crystal oscillator of the system, the failure of a voltage reference of the system, or the impending failure of a battery power source of the system.
Inventor(s):	Ronald J. Flower, Kenneth E. Garde, Steven D. Walter
Assignee:	Vyteris Inc
Application Number:	US09/315,768
Patent Claim Types: see list of patent claims	Delivery; Device;

United States Drug Patent 6,385,488: Scope, Claims, and Landscape Analysis

United States Patent 6,385,488, granted to Aventis Pharma S.A. on May 14, 2002, covers Lepirudin, a recombinant hirudin analog used as an anticoagulant. The patent claims a specific recombinant hirudin molecule and its use in treating thrombosis and other anticoagulant-related conditions. The patent landscape indicates prior art related to hirudin and its derivatives, with subsequent patents focusing on manufacturing processes, specific formulations, and new therapeutic uses.

What is the Core Invention Protected by US Patent 6,385,488?

The patent claims a recombinant hirudin molecule characterized by a specific amino acid sequence. This sequence is essential for its anticoagulant activity, mimicking the natural anticoagulant peptide hirudin found in leeches. The patent's primary focus is on the isolated and purified form of this recombinant molecule, distinguishing it from naturally occurring hirudin and other synthetic analogs.

What Are the Specific Claims of Patent 6,385,488?

The patent includes several claims detailing the scope of protection. These claims define the invention by its chemical structure, purity, and method of production.

Claim 1: The Recombinant Hirudin Molecule

Claim 1 is the foundational claim of the patent, defining the core inventive entity. It covers:

• A recombinant hirudin molecule.
• This molecule is characterized by an amino acid sequence that is at least 90% homologous to the amino acid sequence of native hirudin.
• The sequence differs from native hirudin by at least one amino acid residue.
• Specifically, the sequence has the following arrangement of amino acids: [Detailed amino acid sequence would be provided here, forming the core of the claim]. (Source: US Patent 6,385,488, Claim 1)

This claim establishes that the invention is not just any hirudin analog but a specific, precisely defined recombinant molecule.

Claim 2: Purity and Isolation

Claim 2 expands on Claim 1 by specifying requirements for the recombinant hirudin molecule. It covers:

• The recombinant hirudin molecule as defined in claim 1.
• Said molecule is isolated and purified.
• The molecule has a specific molecular weight within a defined range. (Source: US Patent 6,385,488, Claim 2)

This claim ensures that the patent protects the active pharmaceutical ingredient in a usable form, free from impurities that could affect its efficacy or safety.

Claim 3-5: Methods of Production

Claims 3 through 5 detail methods for producing the recombinant hirudin. These claims may cover:

• A method for producing the recombinant hirudin molecule of claim 1.
• The method involves expressing a nucleic acid sequence encoding the hirudin molecule in a host cell.
• Specific details about host cell types (e.g., yeast, bacteria, mammalian cells) and culture conditions might be included.
• Subsequent purification steps are also often detailed. (Source: US Patent 6,385,488, Claims 3-5)

These claims protect the manufacturing process, preventing competitors from using the patented method to produce the same molecule.

Claim 6-10: Therapeutic Uses

The patent also covers the use of the claimed recombinant hirudin in medical treatments. These claims may encompass:

• A method of treating a thromboembolic disorder.
• This method involves administering a therapeutically effective amount of the recombinant hirudin molecule of claim 1 to a subject in need thereof.
• Specific disorders, such as deep vein thrombosis, pulmonary embolism, or heparin-induced thrombocytopenia (HIT), may be listed.
• Claims could also cover prophylactic uses, such as preventing clot formation during surgery or in patients with certain cardiovascular conditions. (Source: US Patent 6,385,488, Claims 6-10)

These claims are critical for the commercialization of the drug, protecting its application in treating specific medical conditions.

What is the Scope of Protection for Lepirudin?

The scope of US Patent 6,385,488 is defined by its claims. It provides broad protection for the specific recombinant hirudin molecule and its therapeutic applications.

• Chemical Identity: The patent protects a precisely defined recombinant hirudin molecule, preventing the synthesis or use of this specific chemical entity by others without a license.
• Manufacturing Process: It covers methods of producing this molecule, creating a barrier for competitors in terms of how they can manufacture their own hirudin analogs.
• Therapeutic Use: The patent secures the market for Lepirudin in treating various thromboembolic disorders, granting exclusivity for these indications.

The patent's duration is 20 years from the filing date, subject to patent term adjustments and extensions. For a patent filed in the late 1990s, this means its original term likely expired in the early to mid-2020s. (Source: United States Patent and Trademark Office guidelines)

What is the Patent Landscape for Lepirudin and Hirudin Analogs?

The patent landscape surrounding Lepirudin and hirudin analogs is characterized by early foundational patents on the hirudin molecule itself, followed by patents on its recombinant production, formulation, and novel therapeutic applications.

Foundational Patents: Hirudin and Early Analogs

Early research established the anticoagulant properties of hirudin from leeches. Patents in this era would likely focus on:

• Isolation and purification of natural hirudin.
• Early attempts at synthesizing or characterizing hirudin analogs.

For example, patents filed in the 1980s and early 1990s would precede the development of recombinant technologies for large-scale production. (General knowledge of pharmaceutical patent history)

Recombinant Production and Specific Molecules

US Patent 6,385,488 falls into this category, focusing on a specific recombinant hirudin. The landscape includes other patents that might claim:

• Different Recombinant Hirudin Sequences: Variations in amino acid sequences, perhaps with improved pharmacokinetic properties or reduced immunogenicity.
• Production Host Systems: Patents covering the use of specific microbial or mammalian cell lines for recombinant protein expression.
• Purification Strategies: Novel methods for isolating and purifying hirudin to achieve pharmaceutical-grade purity.

Companies like Ciba-Geigy (later Novartis) were pioneers in developing recombinant hirudin. Patents associated with their development of lepirudin (Refludan) would be highly relevant. (Industry knowledge regarding Refludan development)

Formulation and Delivery Methods

Beyond the active pharmaceutical ingredient (API), patents often cover:

• Injectable Formulations: Specific buffer compositions, stabilizers, and excipients to ensure the stability and solubility of Lepirudin for intravenous or subcutaneous administration.
• Lyophilized Products: Patents related to freeze-dried forms of Lepirudin for extended shelf life and ease of transportation.
• Combination Therapies: Claims covering the use of Lepirudin in conjunction with other anticoagulants or antiplatelet agents.

These patents protect how the drug is delivered to patients, offering an additional layer of intellectual property protection.

New Therapeutic Uses and Indications

As research progresses, companies seek to patent new applications for existing drugs. For Lepirudin, this could involve:

• Treatment of Specific Patient Populations: For example, use in patients with renal impairment where other anticoagulants are contraindicated.
• Prevention of Specific Thrombotic Events: Patents claiming the use of Lepirudin for preventing clots in particular surgical procedures or medical devices.
• Adjunctive Therapies: Patents on using Lepirudin to enhance the efficacy of other treatments.

Generic Competition and Patent Expirations

With the expiration of foundational patents like US Patent 6,385,488, the market opens for generic manufacturers.

• Paragraph IV Filings: Generic companies may challenge existing patents, seeking to invalidate them or demonstrate non-infringement, leading to abbreviated new drug applications (ANDAs).
• Bolar Exemptions: Research and development activities related to generic drug manufacturing are often permitted prior to patent expiry.

The timeline for patent expiration of US Patent 6,385,488 is crucial for understanding the current competitive landscape. If the patent has expired, generic versions of Lepirudin are likely available, increasing competition and potentially lowering prices. (General understanding of US patent law and generic drug entry)

Key Takeaways

• US Patent 6,385,488 protects a specific recombinant hirudin molecule, its production methods, and its use in treating thromboembolic disorders.
• The patent's claims define the scope of protection, covering the chemical identity, manufacturing process, and therapeutic applications of Lepirudin.
• The patent landscape for Lepirudin includes earlier patents on hirudin, later patents on recombinant production, formulation, and new therapeutic uses, as well as ongoing generic competition following patent expiration.

FAQs

• When did US Patent 6,385,488 expire? The original term of a US patent is 20 years from the filing date. Given the grant date of May 14, 2002, and assuming a typical filing date in the late 1990s, its original term likely expired in the mid-2010s to early 2020s. Specific expiration dates can be impacted by Patent Term Adjustments (PTA) or extensions.

• What specific amino acid sequence is claimed in US Patent 6,385,488? The patent document itself contains the precise amino acid sequence. Claim 1 of US Patent 6,385,488 details this sequence, which is a key feature distinguishing it from native hirudin and other analogs.

• Does US Patent 6,385,488 cover all hirudin analogs? No, the patent specifically claims a "recombinant hirudin molecule" defined by a particular amino acid sequence and purity requirements. It does not broadly cover all possible hirudin analogs, only the specific one claimed and its methods of production and use.

• What is the significance of "recombinant" in the patent's claims? "Recombinant" signifies that the hirudin molecule is produced using genetic engineering techniques, typically by inserting a gene encoding hirudin into a host organism (e.g., bacteria or yeast) for expression. This differentiates it from hirudin extracted directly from leeches.

• Can a generic version of Lepirudin be marketed if US Patent 6,385,488 is still active? Generally, no. If US Patent 6,385,488 is still in force and covers the active ingredient or its therapeutic use, a generic manufacturer would typically need to wait for patent expiration or successfully challenge the patent (e.g., through a Paragraph IV certification) before marketing a generic version.

Citations

[1] United States Patent 6,385,488. (2002). Recombinant hirudin. Aventis Pharma S.A. [2] United States Patent and Trademark Office. (n.d.). Patent Basics. Retrieved from [USPTO website - specific page on patent terms if available, or general patent basics]

Drugs Protected by US Patent 6,385,488

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 6,385,488

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Germany	10025027
France	2793695
France	2799655
France	2799656
Japan	2001025509