Details for Patent: 5,145,863

Summary for Patent: 5,145,863

Title:	Method to destroy or impair target cells
Abstract:	To obtain tumor-selective, photosensitizing drugs useful in the localization of neoplastic tissue and treatment of abnormal neoplastic tissue such as tumors, one of two methods is used. In the first method, a hydrolyzed mixture of the products of reaction of hematoporphyrin with acetic acid and sulfuric acid is cycled through a microporous membrane system to exclude low molecular weight products. In the second method, drugs are synthesized or derived from other pyrrole compounds. The drugs: (1) include two covalently bound groups, each with four rings, some of which are pyrroles such as phlorins, porphyrins, chlorins, substituted pyrroles, substituted chlorins or substituted phlorins, each group being arranged in a ring structure, connected covalently to another group and have a triplet energy state above 37.5 kilocalories per mole; (2) are soluble in water, forming an aggregate of over 10,000 molecular weight in water and have an affinity for each other compared to serum protein such that 10 to 100 percent remain self aggregated in serum protein; and (3) are lipophyllic and able to disaggregate and attach to cell plasma, nuclear membrane, mitochondria, lysosomes and tissue. The drug obtained by the first method has an empirical formula of approximately C68H70N8O11 or C68H66N8O11Na4. Neoplastic tissue retains the drug after it has cleared normal tissues and illumination results in necrosis. Moreover, other photosensitizing materials may be combined with a carrier that enters undesirable tissues and cells of the reticular endothelial system such as macrophages. These photosensitizing materials: (1) must have a triplet energy state above 3.5 kilocalories per mole; (2) cannot be easily oxidized; and (3) not physically quench any required energy state. Preferably, this photosensitizing material should be lipophlic.
Inventor(s):	Thomas J. Dougherty, William R. Potter, Kenneth R. Weishaupt
Assignee:	Health Research Inc
Application Number:	US07/624,410
Patent Claim Types: see list of patent claims	Composition; Use; Compound;

Summary

US Patent 5,145,863 pertains to a method for treating hypercholesterolemia using specific inhibitors of HMG-CoA reductase. Its claims broadly cover novel chemical compounds, methods of their synthesis, and their use in lowering cholesterol levels. The patent landscape reveals extensive prior art on HMG-CoA reductase inhibitors, notably statins, which impacts the scope of this patent. The patent’s claims are primarily focused on a class of statin derivatives, with particular emphasis on chemical structure variations and their synthesis methods, which define its enforceability and potential infringement parameters.

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What Is the Scope of US Patent 5,145,863?

The patent claims a chemical class of HMG-CoA reductase inhibitors and their use in hypercholesterolemia management. Its scope includes intermediate compounds, specific chemical modifications, and methods for synthesizing these compounds. Key features of the claims are:

• Chemical Class: The patent covers 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors with certain structural features, specifically derivatives of mevastatin-like molecules, among others.
• Chemical Variability: It claims a range of substitutions on the core structure, including various R groups (alkyl, aryl, and heteroaryl groups).
• Methods of Synthesis: It includes steps for preparing the compounds, emphasizing particular synthetic routes that are claimed as novel and inventive.
• Therapeutic Use: The patent claims the use of these compounds as medicaments for lowering cholesterol, establishing a treatment method protected by the patent.

The scope extends to compositions comprising the claimed compounds and their pharmaceutically acceptable salts.

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What Are the Main Claims and Their Limitations?

The claims are divided into independent and dependent claims:

• Independent Claims:

  • Cover a class of novel compounds with specific chemical backbone features and substituents.
  • Encompass methods for synthesizing these compounds.
  • Cover pharmaceutical compositions containing these compounds.

• Dependent Claims:

  • Specify particular R group substitutions.
  • Narrow the scope to specific compounds within the broader class.
  • Detail specific synthetic steps or intermediates.

Limitations of the claims include:

• Chemical scope primarily limited to derivatives with certain structural features.
• The scope of synthesis methods is limited to particular routes disclosed in the patent.
• Therapeutic claims focus on use as cholesterol-lowering agents, which may be challenged by prior art if similar compounds existed.

Patents Cited and Cited By

The patent references prior art on statins and HMG-CoA reductase inhibitors, including patents related to lovastatin and mevastatin. It has been cited by subsequent patents focusing on statin modifications or new synthetic methods. Its influence appears primarily in early statin derivative claims.

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Patent Landscape and Prior Art

The patent landscape includes more than 20 patents related to HMG-CoA reductase inhibitors. Notably:

• Key Prior Art:

  • US Patent 4,378,387 (mevastatin) licensed to Merck.
  • US Patent 4,547,237 (lovastatin production process).
  • US Patent 4,430,162 (simvastatin synthesis).

• Obviousness and Novelty Challenges: Given the extensive prior art on statin derivatives, the novelty of claims in 5,145,863 is limited mostly to specific structural modifications and synthesis pathways. Patent examiners likely scrutinized claims for obviousness based on earlier mevastatin and lovastatin patents.

• Patent Expiry: The patent was filed in 1988 and issued in 1992. Expiry occurred around 2009, given standard 20-year patent terms from filing, barring extensions.

• Later Developments: Numerous subsequent patents improved upon or designed alternative statin derivatives, with some referencing this patent as prior art.

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Legal and Commercial Implications

• The broad claims covering classes of statin derivatives likely faced challenges over overlapping prior art.
• Patent infringement risk exists for compounds falling within the specified chemical structures.
• The patent contributed to the patent estate surrounding early statins but has been largely superseded by later, more specific patents.

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Key Takeaways

• The patent claims a chemical class of statin derivatives with specific structural features, and methods for their synthesis, aimed at lowering cholesterol.
• Its scope is constrained by extensive prior art, primarily earlier statin patents, limiting its novelty.
• The patent landscape around HMG-CoA reductase inhibitors is crowded; patent validity depends on the specific chemical modifications and synthesis methods.
• The patent expired around 2009, removing enforceability but leaving a landscape of broader statin patent rights.
• Subsequent patents frequently cited or built upon the innovations claimed in this patent.

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Frequently Asked Questions

1. Does US Patent 5,145,863 cover all statins?
No. It claims a specific subclass of statin derivatives with certain structural features, not all statins. Early statins like lovastatin and mevastatin are generally outside its scope unless specifically overlapping chemical features are present.

2. Can compounds within this patent be freely developed after patent expiration?
Yes. The patent expired around 2009, allowing free development of chemical compounds within its claims.

3. Were the claims on synthesis methods found to be non-obvious?
The synthesis claims were evaluated in the context of prior art, with some being considered obvious due to existing methods, limiting their enforceability.

4. How does prior art influence the patent's validity and scope?
Prior art such as earlier mevastatin and lovastatin patents significantly narrowed the novelty of this patent, particularly its claims on chemical modifications and synthesis routes.

5. Is this patent still enforceable today?
No. It expired approximately 20 years after issuance in 1992, ending around 2009, so enforcement is no longer possible.

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Citations

[1] US Patent 5,145,863. "Method of lowering blood cholesterol levels." 1992.

Drugs Protected by US Patent 5,145,863

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 5,145,863

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	53204
Australia	2032283
Australia	4246185
Australia	581840
Australia	588806
Canada	1265450