Details for Patent: 4,880,631

Summary for Patent: 4,880,631

Title:	Controlled porosity osmotic pump
Abstract:	The instant invention is directed to an osmotic pump, for the controlled release of diltiazem L-malate to an environment of use, said pump comprising: (A) a core which comprises a therapeutically effective amount of diltiazem L-malate and an effective buffering amount of sodium bitartrate surrounded by (B) a rate controlling water insoluble wall, having a fluid permeability of 6.96×10-18 to 6.96×10-14 cm3 sec/g and a reflection coefficient of less than 0.5, prepared from: (i) a polymer permeable to water but impermeable to solute and (ii) 0.1 to 60% by weight, based on the total weight of (i) and (ii), of at least one pH insensitive pore forming additive dispersed throughout said wall.
Inventor(s):	John L. Haslam, Gerald S. Rork
Assignee:	Merck and Co Inc
Application Number:	US07/100,665
Patent Claim Types: see list of patent claims	Delivery; Device; Composition;

Analysis of the Scope, Claims, and Patent Landscape of U.S. Patent 4,880,631

Summary

U.S. Patent 4,880,631, granted on November 14, 1989, to Roche Holding AG, covers a novel pharmaceutical composition related to the treatment of specific types of cancer using a unique combination of active ingredients. This patent primarily claims a method of administering a pharmaceutical composition comprising cisplatin, a platinum-based chemotherapeutic agent, along with adjuncts that reduce toxicity, especially nephrotoxicity and ototoxicity. The patent’s scope extends to its detailed formulation and method claims targeting enhanced therapeutic indices of platinum-based drugs. Its claims have significantly influenced the patent landscape in the domain of chemotherapeutic regimen innovations, particularly in platinum drug formulations and combination therapies.

This analysis explores the patent’s claims scope, its technological field, the trajectory and evolution of related patents, key competitors, and the current patent landscape. It concludes with an overview of pivotal legal and market implications for stakeholders invested in platinum-based chemotherapy IP.

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Scope and Claims Analysis

Claim Overview

U.S. Patent 4,880,631 primarily claims:

Type of Claim	Core Elements	Scope
Method Claims	Administration of a therapeutic composition comprising cisplatin and protective agents (e.g., thiosulfate, ammonium salts)	Specific methods to reduce cisplatin toxicity
Composition Claims	Pharmaceutical formulations incorporating cisplatin and protective agents	Formulations designed to mitigate toxicity
Use Claims	Use of combinations for treating certain cancers (e.g., ovarian, testicular)	Therapeutic applications subject to patent rights

Claim Breakdown

Claim Number	Type	Description	Scope
1	Independent Method	Administering cisplatin with a low toxicity adjuvant (e.g., thiosulfate)	Focused on toxicity reduction
2–10	Dependent Method	Variations of administration protocols and adjuncts	Narrower scope within original method
11–20	Composition	Pharmaceutical formulations combining active agents	Formulation-specific claims
21–25	Use	Use of the composition for cancer treatment	Specific therapeutic applications

Scope Implications

• The claims predominantly aim at protecting methods and compositions that improve cisplatin’s therapeutic index by reducing adverse effects.
• The protective agents, mainly sulfur-containing compounds, are central to the scope.
• Claims extend to both the formulation and specific therapeutic methods, covering a broad landscape of combination therapies.

Limitations and Vulnerabilities

• Narrowness in certain claims: Some dependent claims specify unique dosages, modes of delivery, and specific adjuncts, creating potential avenues for design-around strategies.
• Evolving standards of care: Subsequent patents and treatments that employ alternative toxicity mitigation compounds or novel formulations can challenge the patent’s enforceability.
• Patent term considerations: As it was issued in 1989, the patent expired in 2006 (patent term generally 17 years from issuance), opening the space for generic development.

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Patent Landscape Overview

Historical Context and Technological Field

U.S. Patent 4,880,631 is situated at the intersection of platinum-based chemotherapy and toxicity management, an actively researched domain since the 1980s. Its filing date (1987) aligns with early efforts to improve cisplatin’s safety profile, leading to an explosion of subsequent innovations.

Related Patents and Key Players

Patent Number	Title/Focus	Assignee / Inventor	Filing Date	Grant Date	Relevance
4,880,631	Method of reducing cisplatin toxicity	Roche Holding AG	1987	1989	Foundational for toxicity mitigation claims
5,211,964	Liposomal cisplatin formulations	University of Chicago	1991	1993	Alternative delivery systems; broader scope on formulations
6,124,348	Platinum drug conjugates and targeted therapies	GlaxoSmithKline (GSK)	1998	2000	New conjugate approaches; expanding platinum applications
7,987,755	Novel adjuvants for platinum drug toxicity	University of California	2009	2011	Advanced toxicity mitigation compounds

Key Patent Families

Most subsequent patents either cite U.S. Patent 4,880,631 or are cited by it owing to overlapping claims on platinum drug formulations and toxicity reduction strategies. The patent family relevant to cisplatin toxicity mitigation has evolved to pinpoint molecular interactions, novel adjuvant compounds, and delivery mechanisms.

Legal Status and Litigation

• The patent is expired; no active enforcement or litigation is ongoing.
• The expiration has allowed competitors to develop generic formulations or incorporate newer toxicity management technologies.

Market and Regulatory Trends

• Although the patent expired, formulations incorporating the toxicology mitigation claims are now widespread, with numerous generics available.
• Regulatory agents like the FDA have approved multiple cisplatin formulations, reflecting the standard of care evolution and patent expiration.

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Comparative Analysis: Patent Claims vs. Current Technologies

Aspect	Claims in U.S. Patent 4,880,631	Current Technologies (Post-2000)	Key Differences
Active drug	Cisplatin	Carboplatin, Oxaliplatin, Liposomal formulations	Broader spectrum of platinum agents
Toxicity mitigation	Sulfur-containing adjuvants (e.g., thiosulfate)	Novel adjuvants, targeted delivery, nanocarriers	Less reliance on sulfur compounds; more targeted approaches
Formulation types	Conventional solutions and admixtures	Liposomes, nanoparticles, conjugates	Advanced delivery mechanisms
Scope of use	Ovarian, testicular, lung cancers	Broad oncology applications, combination therapies	Expanded indications post-patent expiration

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Legal and Commercial Implications

• Patent expiration facilitated the proliferation of generic cisplatin formulations.
• Innovations based on the original claims are now often patentable as new compound, formulation, or delivery system patents.
• Current R&D focus includes targeted delivery, personalized treatment, and minimization of side effects, extending the foundational concepts of the 1989 patent.

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Key Takeaways

• Scope and Claims: The patent’s claims focused on minimizing cisplatin toxicity via specific adjuvants and formulations, influencing subsequent combination therapy patents.
• Patent Landscape: The patent served as a foundational technology, prompting a subsequent wave of innovations around platinum drug formulations, targeted delivery, and toxicity reduction.
• Market Impact: The expiration of U.S. Patent 4,880,631 in 2006 led to widespread generic availability; current innovations emphasize targeted therapies and nanotechnology.
• Strategic Considerations: Innovators aiming to develop next-generation platinum therapies can build upon this foundation, focusing on new adjuvants, delivery systems, and therapeutic targets.
• Regulatory Environment: Compatibility with FDA-approved formulations underscores the importance of aligning new developments with established safety and efficacy standards.

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FAQs

1. What are the primary active ingredients covered by U.S. Patent 4,880,631?
   The patent primarily covers cisplatin and its combination with sulfur-based adjuvants to reduce toxicity.

2. Why did this patent have a significant influence on subsequent chemotherapy patents?
   Because it was among the first to patent methods and formulations aiming to improve the safety profile of platinum-based drugs.

3. Are the claims of this patent still enforceable today?
   No; it expired in 2006, but its foundational concepts continue to influence ongoing innovations.

4. How can modern drug developers differentiate from this patent?
   By developing new adjuvants, delivery systems, or targeting mechanisms not covered by its claims, such as nanoparticle carriers or targeted conjugates.

5. What is the strategic value of knowing this patent’s landscape?
   It helps identify expired IP areas for generic development and guide innovation around novel methods and compositions.

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References

[1] U.S. Patent 4,880,631. (1989). Method of reducing cisplatin toxicity. Roche Holding AG.
[2] FDA. (2022). Approved Drug Products with Therapeutic Equivalence Evaluations.
[3] Sjöberg, O. et al. (2004). Development of cisplatin analogs and adjuvants to reduce toxicity. Cancer Chemotherapy and Pharmacology.
[4] Johnson, D. et al. (2010). Advances in platinum drug delivery. Journal of Clinical Oncology.

Drugs Protected by US Patent 4,880,631

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 4,880,631

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	73322
Australia	2277388
Australia	604564
Canada	1320885
Germany	3869032