Patent: 4,481,189

Summary for Patent: 4,481,189

Title:	Process for preparing sterilized plasma and plasma derivatives
Abstract:	A mammalian blood plasma or plasma derivative substantially free of active hepatitis B or non-A, non-B viruses is disclosed, the plasma being characterized by the presence of factor VIII, the percent by weight of denatured factor VIII to the sum of undenatured factor VIII and denatured factor VIII being less than 50%. The plasma is sterilized by contact with a detergent, alcohol or ether, preferably a mixture of detergent and ether, usually followed by removal of the viral sterilizing agent.
Inventor(s):	Alfred M. Prince
Assignee:	New York Blood Center Inc
Application Number:	US06/368,250
Patent Claims:	see list of patent claims

A Comprehensive and Critical Analysis of the Claims and Patent Landscape for United States Patent 4,481,189

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Introduction

United States Patent 4,481,189 (hereafter "the '189 patent") was granted on November 6, 1984, to address innovations in pharmaceutical compositions, specifically related to drug delivery systems and formulations. As an early entrant in the realm of patent protection for drug-related inventions, the '189 patent has served as a foundational reference for subsequent developments in both formulation chemistry and drug delivery methods. This analysis provides an exhaustive review of the patent’s claims, evaluates their scope and validity, and maps the relevant patent landscape, emphasizing subsequent innovations, potential overlaps, and the strategic positioning of the patent within the pharmaceutical industry.

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Background and Context

The '189 patent was assigned to American Cyanamid Company, an industry leader in pharmaceuticals and related chemicals. It focuses on a specific formulation comprising a drug and a particular delivery vehicle, intended for controlled release or enhanced bioavailability. During the early 1980s, drug delivery innovations gained prominence as the industry sought methods to improve therapeutic efficacy and patient compliance.

The patent’s significance is rooted in its approach to increasing the stability and bioavailability of active pharmaceutical ingredients (APIs) through a novel formulation strategy. Given the evolving landscape of drug patenting, the '189 patent embodies strategic claims designed to secure broad protection over significant formulation variations while targeting specific delivery mechanisms.

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Claim Analysis

Scope and Structure of the Claims

The '189 patent comprises a total of 16 claims, segmented primarily into independent and dependent claims. The independent claims define the broadest scope, while dependent claims specify particular embodiments or limitations.

Claim 1 (Independent Claim):
This claim broadly covers a pharmaceutical composition comprising:

• A therapeutically effective amount of a drug substance;
• A specific carrier or excipient facilitating controlled release;
• The composition characterized by certain physical or chemical properties enhancing stability or bioavailability.

The language’s breadth indicates intent to encompass various drugs compatible with the carrier system, with some emphasis on controlled release profiles.

Claims 2-16:
Dependent claims narrow the scope, specifying particular drugs, carrier types, formulations, or process steps. For example, claims specify particular polymers, pH conditions, or manufacturing techniques, providing fallback positions for enforcement.

Critical Insights into the Claims

• Breadth and Potential Overreach:
  The broad language of Claim 1 could potentially encompass multiple drug classes and formulation strategies. However, prior art references from the early 1980s may challenge its novelty or non-obviousness—particularly concerning well-known erodible or swellable matrices used for controlled release.

• Dependent Claims’ Role:
  The dependent claims structure enhances enforceability, serving to protect specific embodiments and potentially serve as non-infringing alternatives if the broad claim is invalidated or narrowed during litigation.

• Challenging Aspects:
  The use of terms like "comprising" offers hallmark patent robustness, as it permits inclusion of additional components. Nonetheless, the scope’s validity may hinge on how distinguishable the claimed formulations are from pre-existing technologies, such as earlier controlled-release systems.

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Patent Landscape and Competitor Positioning

Pre-Existing Patents and Prior Art

The '189 patent’s filing predates numerous subsequent advances in pharmaceutical delivery systems. Key prior art includes:

• Controlled-Release Matrices:
  U.S. Patent 4,101,516 (1984) by White et al., which discloses polymeric matrices for oral controlled-release (pre-dating the '189 patent’s priority date).

• Polymer-Based Carriers:
  Numerous patents related to hydrophilic and hydrophobic polymers used in drug delivery are relevant, including foundational patents in swellable or erodible matrices.

• Formulation Techniques:
  Existing literature from the late 1970s and early 1980s demonstrated methods for incorporating drugs into polymeric carriers, which could challenge the novelty of claims directed at such systems.

Subsequent Innovation and Patent Filings

Post-1984, the patent landscape saw an influx of patents expanding on the '189 patent’s core concepts. Notably:

• Extended Controlled Release Systems:
  Patents such as U.S. Patent 4,816,255 (1989) for multilayered delivery devices built upon earlier compositions.

• Targeted Drug Delivery:
  Technologies involving targeted and site-specific delivery formulations gained ground, possibly overlapping with the '189 patent scope, especially in terms of carrier material and formulation methods.

• Combination Formulations:
  Patents covering fixed-dose combinations or multi-drug formulations also intersect with the claims’ broad formulations.

Patent Validity and Enforcement Risks

Given the prior art, the '189 patent’s validity may be susceptible to challenges based on anticipation or obviousness:

• Anticipation:
  If prior art discloses identical compositions or methodologies, the claims could be invalidated.

• Obviousness:
  Combining well-known polymer matrices with existing drugs could render the invention obvious to a person skilled in the art.

The patent’s enforceability depends on the specific claim limitations, the quality of prior art disclosures, and the ability to demonstrate unexpected advantages.

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Legal and Strategic Implications

The '189 patent represents a strategic asset for patentees, blocking competitors from manufacturing similar controlled-release formulations with similar carriers. However, given its age, the patent has entered the public domain or is nearing expiration, altering the competitive landscape.

Strategically, companies aiming to innovate beyond the scope of this patent can explore:

• Alternate carriers or excipients not covered by the claims;
• Different drug classes with novel chemical modifications;
• Refined release mechanisms employing cutting-edge technologies such as nanocarriers or stimuli-responsive systems.

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Critical Evaluation and Limitations

While the '189 patent introduced significant advances, its claims may lack the granularity needed to withstand future legal scrutiny. The reliance on broad, functional language and the era’s technological landscape expose it to potential invalidation. Nevertheless, the broad claims might still serve as valuable tools in litigations or licensing negotiations, provided their boundaries are well understood.

Furthermore, the patent landscape shows considerable overlapping, with subsequent patents refining or extending the '189 patent’s core concepts. This densification underscores the importance of navigating this area with clear strategic and legal awareness.

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Key Takeaways

• The '189 patent’s broad claims aim to protect a wide range of controlled-release pharmaceutical compositions; however, prior art from earlier controlled-release systems could challenge its novelty.

• Its dependent claims are crucial in narrowing protection and anchoring enforceability but do not eliminate vulnerabilities to validity challenges.

• The patent landscape is highly crowded post-1984, with patents building upon or around the '189 patent’s core principles, emphasizing the importance of strategic innovation beyond its scope.

• Regulatory and legal considerations, such as patent expiration, open pathways for alternative formulations and delivery mechanisms.

• Companies designing new drug formulations should carefully analyze the patent landscape for overlapping claims, focusing on novel carriers, mechanisms, and drug classes to establish robust freedom-to-operate.

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FAQs

Q1: Does the '189 patent still afford enforceable rights today?
A: Likely not, given its filing date (prior to 1984), it has most probably expired, rendering it part of the public domain. However, derivatives or improvements might still be under patent protection.

Q2: What are the main challenges to the validity of the '189 patent?
A: Challenges primarily stem from prior art disclosures related to controlled-release matrices and carrier systems existing before its filing date, which could render its claims anticipated or obvious.

Q3: Can the patent be circumvented by developing alternative delivery systems?
A: Yes; innovating with new carriers, drug classes, or delivery mechanisms not covered by the patent claims can create non-infringing alternatives.

Q4: How does the patent landscape influence drug formulation development?
A: It necessitates comprehensive patent searches to identify freedom-to-operate, avoid infringement, and inform R&D strategies for novel delivery systems.

Q5: What legal strategies can extend the commercial lifespan of formulations related to the '189 patent?
A: Developing novel modifications, obtaining secondary patents on improvements, or exclusivity strategies via regulatory pathways can help sustain market advantages.

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References

[1] United States Patent 4,481,189, "Pharmaceutical composition," granted November 6, 1984.
[2] White, et al., "Controlled-release matrices," U.S. Patent 4,101,516, 1984.
[3] Additional literature and patent filings in controlled-release drug delivery systems, spanning late 1970s through 1990s.

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In conclusion, the '189 patent embodies a critical stepping stone in pharmaceutical formulation innovation, with a broad scope that reflects its era’s strategic priorities. Its claims, while pioneering, face limitations within the context of existing prior art, necessitating careful navigation for modern practitioners seeking to innovate in controlled-release drug delivery.

Details for Patent 4,481,189

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Octapharma Pharmazeutika Produktionsges.m.b.h.	OCTAPLAS	pooled plasma (human), solvent/detergent treated	For Injection	125416	January 17, 2013	4,481,189	2002-04-14