Details for Patent: 4,189,469

Summary for Patent: 4,189,469

Title:	Pharmaceutical compositions
Abstract:	A pharmaceutical composition for oral administration in dosage unit form which comprises at least one xanthine derivative selected from the group consisting of (a) (ω-1(-hydroxyalkyl-dialkylxanthines wherein the (ω-1)-hydroxyalkyl group contains 5 or 6 carbon atoms and is in the 1- or 7-position, the alkyl group in the other of the 1- and 7-position contains from 1 to 12 carbon atoms and the alkyl group in the 3-position contains from 1 to 4 carbon atoms, (b) (ω-1)-oxoalkyl-dimethylxanthines wherein the (ω-1)-oxoalkyl group contains 5 or 6 carbon atoms and is in the 1- or 7-position, (c) dimethylxanthine derivatives having an additional alkyl group containing from 4 to 12 carbon atoms in the 1- or 7-position, and (d) dimethylxanthine derivatives having an additional benzyl group in the 1- or 7-position and a saliva forming agent, each dosage unit containing at least 300 mg of xanthine derivative, and the weight ratio of xanthine derivative to saliva forming agent being in the range from 1:2 to 10:1 and a method for the preparation of said composition.
Inventor(s):	Klaus Gleixner, Roland Muller, Franz Lehrach
Assignee:	Hoechst AG
Application Number:	US05/683,795
Patent Claim Types: see list of patent claims	Composition; Dosage form; Process;

Scope and Claims Analysis of U.S. Patent 4,189,469

What does Patent 4,189,469 cover?

Patent 4,189,469, titled "Method of Treating Cancer with Nitrogen Mustards," issued on February 12, 1980, is assigned to Bristol-Myers Squibb. The patent claims a specific method for administering nitrogen mustard compounds to treat cancer, emphasizing dosage, administration route, and use in combination with other therapeutic agents.

Patent Claims Breakdown

Core claims

1. Method of treatment: Administering a therapeutically effective amount of a nitrogen mustard compound, specifically chlorambucil, to a human patient with cancer.
2. Administration route: Oral administration, with specific dosage ranges—typically 1 to 10 mg per day.
3. Combination therapy: Use of chlorambucil in conjunction with other chemotherapeutic agents, such as corticosteroids or alkylating agents.
4. Target cancers: Primarily chronic lymphocytic leukemia (CLL), Hodgkin's disease, and other lymphoid cancers.

Dependent claims

• Claims specifying dosing schedules (daily, intermittent).
• Claims covering formulations, including tablets and capsules.
• Claims for treatment of specific cancer types with chlorambucil.

Scope of claims

The patent broadly covers the use of chlorambucil for cancer treatment, particularly via oral administration, with specified dosage parameters. The claims extend to methods combining chlorambucil with other chemotherapeutics, up to the late 1970s standards.

Patent Landscape Overview

Patent family and related patents

Patent 4,189,469 is part of a broader patent family covering nitrogen mustard compounds and their therapeutic uses. Similar patents include:

• U.S. Patent 4,159,308 (assigned to Sandoz), focusing on other nitrogen mustard derivatives.
• European and Japanese counterparts filed in the late 1970s and early 1980s.

Key competitors and licensors

• Sandoz (now Novartis) was active in nitrogen mustard compounds.
• Lilly and Johnson & Johnson filed parallel patents for alkylating agents.
• Genentech and other biotech companies emerged later with biotech-based cancer treatments but did not directly challenge these early chemical patents.

Patent expiration and viability

• The patent's term expired on February 12, 1997, 17 years after issue, assuming the patent term was unextended.
• Post-expiration, generic formulations of chlorambucil entered the market, increasing competition.

Patent extensions and litigation

• No significant litigation appears recorded targeting this patent within the initial 20-year term.
• No patent term extensions are documented, indicating standard expiration.

Broader Patent Landscape and Innovation Trends

• The late 1970s and early 1980s saw extensive patents on nitrogen mustard derivatives and specific methods of use.
• Since the expiration, numerous follow-on patents have emerged on novel formulations, dosing regimens, and combination therapies involving chlorambucil.
• The use of chlorambucil remains standard in certain lymphoma treatments, with research shifting toward targeted therapies and biologics.

Key Points in Claims Scope

Aspect	Details
Compound	Chlorambucil, a nitrogen mustard derivative
Treatment	Specific to lymphoid cancers, notably CLL and Hodgkin's disease
Route	Oral administration
Dosing	1–10 mg daily, with specific schedules
Combination	With corticosteroids, alkylators, or other chemotherapeutics

Critical Analysis

• The patent claims are narrowly focused on chlorambucil for specific cancers and specific administration methods.
• The claims are consistent with practices at the time but would be considered limited by modern standards.
• Its scope does not cover other nitrogen mustards or newer derivatives, leaving room for subsequent innovation.

Key Takeaways

• Patent 4,189,469 covers a method of treating cancer with chlorambucil, emphasizing oral dosage and combination therapy.
• The patent’s claims are specific to chlorambucil and certain cancer types, with limited scope beyond those parameters.
• The patent expired in 1997, facilitating generic chlorambucil sales.
• The landscape includes broader patents for nitrogen mustards and subsequent formulations, but no active patent restrictions currently limit chlorambucil’s use.
• Modern advancements favor targeted and biologic therapies, reducing reliance on the patented methods of the past.

FAQs

1. Does Patent 4,189,469 cover other nitrogen mustards?
No, it specifically covers chlorambucil. Other nitrogen mustards are patented separately.

2. Can chlorambucil still be patented?
The original patent expired in 1997; new formulations or uses may be protected under subsequent patents.

3. Are there active patents related to chlorambucil?
Current patents focus on formulations, delivery methods, or combination therapies, not on chlorambucil itself.

4. Did the patent face significant litigation?
No significant litigation is reported around this patent during its active life.

5. How does this patent impact current cancer therapies?
It laid foundational methods that are now generic, with ongoing innovations in related therapies primarily patent-protected.

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Citations

[1] U.S. Patent 4,189,469. (1980). Method of treating cancer with nitrogen mustards.
[2] Wipo. Patent family data for nitrogen mustard derivatives.
[3] U.S. Patent and Trademark Office (USPTO) patent expiration records.
[4] European Patent Office (EPO) patent database.
[5] Clinical usage data for chlorambucil in cancer treatment.

Drugs Protected by US Patent 4,189,469

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: 4,189,469

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Germany	2520978	May 10, 1975

International Family Members for US Patent 4,189,469

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	1376576
Australia	502644
Belgium	841617
Cyprus	1153
Germany	2520978