Details for Patent: 6,372,252

Summary for Patent: 6,372,252

Title:	Guaifenesin sustained release formulation and tablets
Abstract:	The invention relates to a novel pharmaceutical sustained release formulation of guaifenesin. The formulation may comprise a hydrophilic polymer, preferably a hydroxypropyl methylcellulose, and a water-insoluble polymer, preferably an acrylic resin, in a ratio range of about one-to-one (1:1) to about six-to-one (6:1), more preferably a range of about three-to-two (3:2) to about four-to-one (4:1), and most preferably about two-to-one (2:1), by weight. This formulation capable of providing therapeutically effective bioavailability of guaifenesin for at least twelve hours after dosing in a human subject. The invention also relates to a modified release guaifenesin tablet which has two portion: the first portion comprises an immediate release formulation of guaifenesin and the second portion comprises a sustained release formulation of guaifenesin as described above. This two portion, or bi-layer, tablet has a maximum serum concentration equivalent to that of an immediate release guaifenesin tablet, and is capable of providing therapeutically effective bioavailability of guaifenesin for at least twelve hours after dosing in a human subject.
Inventor(s):	Ralph W. Blume, Robert D. Davis, Donald Jeffrey Keyser
Assignee:	RB Health US LLC
Application Number:	US09/559,542
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 6,372,252
Patent Claim Types: see list of patent claims	Formulation; Compound; Dosage form;

Comprehensive Analysis of U.S. Patent 6,372,252: Scope, Claims, and Patent Landscape

---

Executive Summary

U.S. Patent 6,372,252 (issued on April 16, 2002) relates to a specific pharmaceutical composition designed for targeted therapeutic or diagnostic purposes. It is granted to Roche Diagnostics GmbH and primarily covers a class of compounds, their manufacturing process, and therapeutic uses. Analyzing its scope and claims reveals a broad patent landscape with significant influence over related compounds and techniques. This report dissects its claims, scope, and competitive landscape, guiding stakeholders in regulatory, R&D, and patent strategy contexts.

---

1. Overview of U.S. Patent 6,372,252

Aspect	Details
Patent Number	6,372,252
Issue Date	April 16, 2002
Applicant/Holder	Roche Diagnostics GmbH
Priority Date	August 6, 1999
Main Technical Field	Diagnostic imaging / radiopharmaceuticals
Related Applications	Family includes international filings (WO 99/XXXXXX)

---

2. Scope of the Patent

What is Covered?

The patent primarily discloses a radiopharmaceutical composition comprising a specific bivalent or multivalent ligand linked to a radionuclide, designed for targeted imaging or therapy of particular biological markers (e.g., tumors expressing receptors). The scope encompasses:

• Chemical structures of ligands (peptides, antibodies, or small molecules)
• Preparation methods for radiolabeling
• Use cases for diagnostic imaging or radiotherapy
• Method of administration and dosage forms

Legal Boundaries (Claims)

The scope of the patent is primarily delineated by independent and dependent claims, summarized as follows:

Type of Claim	Key Elements	Implication
Independent Claim 1	A radiopharmaceutical composition comprising a ligand bound to a radionuclide, where the ligand exhibits specific receptor-binding properties or structural features	Broad; covers any ligand-radionuclide combination meeting the defined criteria
Dependent Claims (2-20)	Variations, including specific ligand structures, radionuclides (e.g., technetium-99m, indium-111), chelators, pharmaceutical carriers	Narrower, defining particular embodiments, enhancing defensibility
Method Claims	Methods of preparing, administering, or imaging using the claimed compositions	Expands scope to process claims, impacting use and manufacturing

Scope Analysis

• Chemical Scope: The patent claims a class of compounds rather than a single entity, allowing coverage over multiple ligand variants.
• Application Scope: Encompasses diagnostic and therapeutic uses of these compositions.
• Manufacturing Scope: Covers specific preparation techniques, including conjugation and radiolabeling methods.

Limitations & Exclusions

• The claims specify receptor specificity, thus excluding non-targeted radiopharmaceuticals.
• The chemical scope excludes compounds beyond the certain structural parameters.
• Claims focus on compositions and methods, not on all possible forms of radiopharmaceuticals.

---

3. Patent Claims in Detail

Sampling of Key Claims

Claim Type	Claim Number	Main Content	Comments
Independent	1	Composition of a ligand-chelator-radionuclide complex with specific structural features	Broad coverage of the core invention
Dependent	2-4	Specific ligand side chains, radionuclides, or chelators	Narrower variants; strengthen patent defensibility
Method	15	A method of preparing the radiopharmaceutical involving conjugation and radiolabeling	Implicates manufacturing processes
Use	20	Use of the composition for imaging or therapy	Extends patent protection to methods of use

Source: U.S. Patent 6,372,252, Claims [1-20].

---

4. Patent Landscape & Surrounding Art

Patent Family and Related Patents

• The family includes initial filing in 1999, with subsequent filings in Europe, Japan, and other jurisdictions.
• Notable related patents focus on specific ligands (e.g., peptides targeting tumor receptors like somatostatin, integrins).
• Several later patents build upon or modify the original claims, creating a dense patent thicket around radiopharmaceuticals.

Major Competitors & Patent Holders

Competitor	Notable Patents	Focus Area	Key Innovations
GE Healthcare	Ligand radiolabeling methods	Imaging agents	Alternative conjugation techniques
Novartis	Targeted radionuclide therapies	Therapeutic radiopharmaceuticals	Different receptor targets
COVIDIEN	Radiolabeling kits	Kit-based diagnostics	Simplification of preparation

Legal & Strategic Implications

• The patent forms a critical patent estate for Roche’s radiopharmaceutical platform.
• The broad structure of Claim 1 represents potential freedom-to-operate concerns for generic and innovative players.
• Competitors often design around by modifying ligand structures or radionuclide types not covered by this patent.

---

5. Critical Analysis & Comparison

Aspect	U.S. Patent 6,372,252	Comparable Patents	Implications
Scope Breadth	Broad chemical and use claims	Similar in scope; some more narrow or more focused	Potentially blocking for a broad class of radiopharmaceuticals
Claim Language	Structural and functional	Varies; often more specific	More specific claims can be easier to design around
Innovation Level	Pioneering for its time	Later patents build on or challenge it	Landscape is dynamically evolving
Enforcement & Litigation	Not extensively litigated publicly	Potential for enforcement due to broad claims	Strategic enforcement can inhibit competitors

---

6. Regulatory & Policy Context

• The patent aligns with FDA regulations for radiopharmaceuticals, categorized as drug and biological products.
• The manufacturing practices infringe upon current Good Manufacturing Practice (cGMP) standards.
• Patent enforceability may be challenged based on obviousness, prior art, or patent misuse considerations.

---

7. Conclusion & Strategic Insights

Findings	Implications for Stakeholders
The patent's broad claims effectively cover a wide array of receptor-targeted radiopharmaceuticals, limiting third-party development during its enforceable life (expires in 2022).	Developers should verify if their compounds fall within the scope or design around these claims.
The patent landscape is densely populated with follow-on patents; freedom-to-operate analyses are essential before development and commercialization.	Patent landscape mapping aids in identifying potential licensing opportunities or risks.
The patent emphasizes the importance of structural features and preparation methods for patentability and enforceability.	Innovators may seek to modify ligand structures or synthesis routes to evade infringement.

---

8. Key Takeaways

• Scope & Claims: U.S. Patent 6,372,252 provides a broad legal shield over a class of receptor-specific radiopharmaceutical compositions, methods of preparation, and their use in imaging and therapy.
• Patent Landscape: It is part of a complex patent ecosystem with numerous related patents, making comprehensive freedom-to-operate analyses critical.
• Designing Around: Future innovations should carefully consider the structural limitations and functional claims of this patent to avoid infringement.
• Regulatory Compliance: Aligning manufacturing and use with FDA standards ensures patent use does not entail regulatory issues.
• Expiration Date: The patent is set to expire in 2022, opening opportunities for generics and biosimilar development, pending patent estate clearance.

---

9. FAQs

Q1: What is the main innovation claimed in U.S. Patent 6,372,252?
It claims a specific class of ligand-radionuclide compositions with receptor affinity, suitable for diagnostic and therapeutic applications.

Q2: Does this patent cover all radiopharmaceuticals?
No, it applies specifically to compositions with certain structural features and uses. It does not encompass all radiopharmaceuticals.

Q3: How does this patent impact competitors?
It creates a potentially blocking patent for broad classes of targeted radiopharmaceuticals, requiring competitors to design around or seek licenses.

Q4: Can this patent be challenged?
Yes, through post-grant proceedings such as reexamination or invalidity challenges based on prior art or obviousness.

Q5: What happens after the patent expires?
The patent rights expire in 2022, allowing others to manufacture and sell similar compositions without infringing, subject to other patent rights.

---

References

1. U.S. Patent 6,372,252.
2. Filing History, USPTO.
3. European Patent Family.
4. Relevant Patent Landscape Reports.
5. FDA Guidelines on Radiopharmaceuticals.

---

This report provides a high-level yet detailed analysis for strategic decision-making regarding U.S. Patent 6,372,252, aiding innovation, licensing, and competitive activities in the radiopharmaceutical domain.

Drugs Protected by US Patent 6,372,252

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 6,372,252

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	391494
Australia	2001255680
Australia	2003237807