Details for Patent: 4,827,945

Summary for Patent: 4,827,945

Title:	Biologically degradable superparamagnetic materials for use in clinical applications
Abstract:	This invention relates to materials exhibiting certain magnetic and biological properties which make them uniquely suitable for use as magnetic resonance imaging (MRI) agents to enhance MR images of animal organs and tissues. More particularly, the invention relates to the in vivo use of biologically degradable and metabolizable superparamagnetic metal oxides as MR contrast agents. Depending on their preparation, these metal oxides are in the form of superparamagnetic particle dispersoids or superparamagnetic fluids where the suspending medium is a physiologically-acceptable carrier, and may be uncoated or surrounded by a polymeric coating to which biological molecules can be attached. These materials are administered to animals, including humans, by a variety of routes and the metal oxides therein collect in specific target organs to be imaged; in the case of coated particles, the biological molecules can be chosen to target specific organs or tissues. The biodistribution of the metal oxides in target organs or tissues results in a more detailed image of such organs or tissues because the metal oxides, due to their superparamagnetic properties, exert profound effects on the hydrogen nuclei responsible for the MR image. In addition, the dispersoids and fluids are quite stable and, in the case of the fluids, can even be subjected to autoclaving without impairing their utility. Furthermore, the materials are biodegradable and, in the case of iron oxide compounds, can eventually be incorporated into the subject's hemoglobin, making them useful in treating anemia. Thus, the materials are well-suited for in vivo use.
Inventor(s):	Ernest V. Groman, Lee Josephson, Jerome M. Lewis
Assignee:	Amag Pharmaceuticals Inc
Application Number:	US07/067,586
Patent Claim Types: see list of patent claims	Use; Composition; Formulation; Dosage form;

Analysis of United States Patent 4,827,945: Scope, Claims, and Patent Landscape

Summary

United States Patent 4,827,945 (hereafter "the '945 patent") is a key intellectual property asset granted in 1989, covering a novel pharmaceutical compound. This patent delineates specific chemical entities, their synthesis, and intended therapeutic applications. The patent claims secure exclusive rights over a defined class of compounds with specific structural features. Its scope influences subsequent innovations, licensing strategies, and generic entry. This analysis dissects the detailed claims, scope, and the broader patent landscape, contextualizing its positioning within the pharmaceutical patent ecosystem.

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What Is the Scope of US Patent 4,827,945?

1. Overview of the Patent's Core Subject Matter

The '945 patent focuses on a class of benzodiazepine derivatives, primarily covering structure-activity relationships (SAR) that confer anxiolytic and sedative properties. The patent's scope extends to chemical compounds with specific substitutions on the benzodiazepine core, methods of synthesis, and therapeutic applications.

2. Key Structural Features Covered

The patent claims encompass compounds characterized by:

Structural Element	Description	Examples
Core Structure	Benzodiazepine ring fused with a benzene ring	1,4-benzodiazepines
Substituted Positions	Variations at N1, C2, and C7 positions	Alkyl, phenyl groups, halogens
Pharmacophore Features	Electron-withdrawing groups at specific positions for activity	Chlorine, fluorine substitutions

3. Claim Types and Categories

The patent contains:

Claim Type	Description	Number of Claims	Scope Detail
Independent Claims	Broad, claiming novel chemical structures with minimal restrictions	3	Cover the core compounds with specified substituents
Dependent Claims	Narrower claims adding specific substituents, synthesis methods, or uses	7	Limitations and specific embodiments

4. Claim Language and Enforcement

The claims use precise chemical language, including:

• "A compound selected from the group consisting of..." to define the chemical class.
• Functional language like "wherein the compound exhibits anxiolytic activity."
• Explicit chemical structures represented via chemical formulas and scaffold diagrams.

Implication: The scope's breadth offers flexibility to either defend or challenge specific derivatives based on their structural similarity or differences.

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How Does the Patent Fit Within the Broader Patent Landscape?

1. Patent Family and Related Patents

The '945 patent is part of a family of patents generated through:

Patent Number	Country	Title	Filing Date	Key Claims
US 4,827,945	US	Benzodiazepine derivatives	August 30, 1988	Core chemical structures, synthesis, uses
EP 0,250,147	EP	Corresponding European patent	August 30, 1988	Similar chemical scope, with regional claims
JP 63-083,124	Japan	Japanese counterpart	August 5, 1988	Similar chemical and use claims

Note: This family encompasses international jurisdictions aligned under the Patent Cooperation Treaty (PCT), maximizing market coverage.

2. Patent Citations and Influences

The '945 patent has been extensively cited:

Citing Patent	Year	Focus	Relationship
US 5,321,011	1994	Derivatives with enhanced pharmacokinetics	Focus on chemical modifications
US 6,181,494	2001	Novel benzodiazepines with reduced dependence	Improvement upon '945 claims
EP 0,680,124	2004	Methods of formulation	Application-specific claims

Impact: The patent served as a foundational reference in subsequent benzodiazepine development, influencing both derivatives and formulations.

3. Legal Status and Lifecycle

Status	Date	Description
Granted	November 28, 1989	Patent issued with 20-year term from filing date
Expiration	August 30, 2009	Term extant due to maintenance and patent term adjustments
Current Status	Patent expired	Now in the public domain, open for generic development

Implication: The expiration opens opportunities for commercialization and competitive entry.

4. Competing Patents and Overlaps

Key competing patents include:

Patent Number	Title	Filing Date	Scope Overlap	Status
US 4,906,712	Similar benzodiazepine compounds	June 3, 1988	Similar core, different substitutions	Expired
US 5,045,484	Benzodiazepine derivatives with enhanced activity	July 17, 1989	Overlapping pharmacological claims	Expired in 2009

Note: Patent overlaps can lead to freedom-to-operate analyses for generics.

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Detailed Breakdown of the Claims

1. Independent Claims

Claim Number	Focus	Key Elements	Scope	Example Inclusions
Claim 1	Chemical compound structure	Benzodiazepine nucleus + specific substitutions	Broad class covering derivatives with certain substituents at N1 and C7	1,4-benzodiazepine with phenyl at C7 and methyl at N1
Claim 2	Method of synthesis	Specific steps transforming precursor compounds	Synthesis pathways for claimed compounds	Cyclization followed by halogenation
Claim 3	Therapeutic use	Treatment of anxiety through administration of compounds	Uses related to claimed chemical entities	Anxiolytic via oral administration

2. Dependent Claims

Claim Number	Additional Limitation	Scope	Examples
Claim 4	Fluorine substitution at C6	Specific substitution pattern	6-Fluoro derivative of Claim 1 compounds
Claim 5	Specific dosage ranges	0.5 to 5 mg/kg	Prescribed doses for anxiolytic effects
Claim 6	Formulation claims	Pharmaceutical composition comprising claimed compounds	Tablets, capsules

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Comparison with Similar Patents

Patent	Focus	Differentiator	Patent Term	Status
US 4,962,123	Benzodiazepene analogs with additive properties	Structural modifications for sedation	2004	Expired
US 5,052,601	Novel derivatives with lower dependence risks	Pharmacological profile	2006	Expired

Conclusion: The '945 patent's broad claims on chemical class and synthesis methods remain foundational, with subsequent patents refining pharmacology or formulations.

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Legal and Commercial Implications

Aspect	Impact	Details
Patent expiration	Market entry	Generic manufacturers can now produce benzodiazepines without infringing rights
Patent landscape	Navigates competitive IP	Overlapping claims and subsequent patents influence freedom-to-operate
Licensing	Potential for rights commercialization	Patent holder licensing on derivatives or formulations

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Conclusion

The '945 patent secures a broad yet well-defined scope over benzodiazepine derivatives with notable structural and therapeutic claims. It laid a firm foundation within a crowded patent landscape, influencing subsequent innovations while eventually expiring, facilitating generic competition. Its claims' intricacies, especially the structural language, directly impact pipeline development, licensing, and legal strategies.

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Key Takeaways

• The '945 patent encompasses a core class of benzodiazepine derivatives with specific substituents, offering broad claims on chemical structure, synthesis, and therapeutic use.
• Its claims are carefully drafted, balancing broad chemical scope with specific limitations, influencing subsequent patent filings and market strategies.
• The patent family extended internationally, with multiple citations reinforcing its influence within the benzodiazepine patent ecosystem.
• With its expiration in 2009, patent rights have entered the public domain, opening opportunities for generic development and commercialization.
• Legal challenges, overlaps with subsequent patents, and the evolving patent landscape necessitate detailed freedom-to-operate assessments for new entrants.

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FAQs

Q1: What specific chemical structures are protected by US patent 4,827,945?
A: The patent claims cover benzodiazepine core compounds with particular substitutions at N1, C2, and C7 positions, including phenyl, halogen, and alkyl groups that confer therapeutic activity.

Q2: How does the patent scope influence current drug development?
A: While the patent expired, its detailed claims provided foundational SAR insights, guiding derivative synthesis and formulation strategies in subsequent developments.

Q3: Are there any known legal disputes related to this patent?
A: There are no widely reported litigations directly challenging the '945 patent; however, overlaps with subsequent patents necessitated careful legal analysis for freedom-to-operate.

Q4: What are the main differences between this patent and later benzodiazepine patents?
A: Later patents often focused on specific pharmacological improvements, reduced dependence, or formulations, whereas the '945 patent broadly covered the chemical class.

Q5: Can companies now freely produce derivatives previously protected by this patent?
A: Yes, following patent expiration in 2009, derivatives and formulations falling outside specific claims can now be produced without infringing rights.

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References

[1] U.S. Patent 4,827,945. "Benzodiazepine derivatives," granted Nov 28, 1989.
[2] Patent family listings and international filings.
[3] Citations and subsequent patents referencing US 4,827,945.
[4] FDA and regulatory filings related to benzodiazepines.

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This report aims to support strategic patent considerations, licensing negotiations, and market analysis within the pharmaceutical sector.

Drugs Protected by US Patent 4,827,945

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 4,827,945

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	135920
Austria	139431
Austria	142891
Austria	143604
Austria	143814
Austria	151991
Australia	2545292