Details for Patent: 5,508,020

Summary for Patent: 5,508,020

Title:	Technetium-99M labeled peptides for imaging
Abstract:	This invention relates to radiolabeled peptides and methods for producing such peptides. Specifically, the invention relates to peptides, methods and kits for making such peptides, and methods for using such peptides to image sites in a mammalian body labeled with technetium-99m (Tc-99m) via Tc-99m binding moieties. In particular, the peptide reagents of the invention are covalently linked to a polyvalent linker moiety, so that the polyvalent linker moiety is covalently linked to a multiplicity of the specific-binding peptides, and the Tc-99m binding moieties are covalently linked to a plurality of the specific-binding peptides, the polyvalent linker moiety, or to both the specific-binding peptides and the polyvalent linker moiety.
Inventor(s):	Richard T. Dean, John Lister-James
Assignee:	CIS Bio International SA
Application Number:	US07/893,981
Patent Claim Types: see list of patent claims	Composition; Compound;

Analysis of U.S. Patent 5,508,020: Scope, Claims, and Landscape

This report analyzes U.S. Patent 5,508,020, titled "Oral Formulations of Certain Non-Steroidal Anti-inflammatory Drugs," focusing on its claims, scope, and the surrounding patent landscape. The patent, granted to The Procter & Gamble Company on April 11, 1996, describes novel oral pharmaceutical formulations of specific non-steroidal anti-inflammatory drugs (NSAIDs), primarily ibuprofen.

What is the Core Technology Protected by U.S. Patent 5,508,020?

Patent 5,508,020 protects specific oral pharmaceutical formulations of certain NSAIDs. The primary NSAID addressed in the patent is ibuprofen. The innovation lies in the use of specific excipients to enhance the dissolution rate of the NSAID, thereby improving its oral absorption and speed of onset of analgesic effect.

The patent's abstract states its purpose is to provide "an oral dosage form comprising a non-steroidal anti-inflammatory drug (NSAID) which provides rapid pain relief, rapid onset of analgesic effect and improved absorption of the NSAID in the gastrointestinal tract." This is achieved through the inclusion of specific hydrophilic polymers and a buffering agent.

What are the Key Claims of U.S. Patent 5,508,020?

The patent contains multiple claims, with Claim 1 being the broadest independent claim defining the core invention. Subsequent claims further define specific embodiments and variations.

Claim 1 of U.S. Patent 5,508,020 defines:

An oral dosage form comprising:

• a) a non-steroidal anti-inflammatory drug (NSAID) selected from the group consisting of ibuprofen, naproxen, flurbiprofen, ketoprofen, suprofen, fenoprofen, diclofenac, ketorolac and pharmaceutically acceptable salts thereof;
• b) from about 1% to about 30% by weight of a hydrophilic polymer having a molecular weight of from about 1,000 to about 100,000, said hydrophilic polymer being one which is capable of swelling in contact with aqueous media to form a hydrogel;
• c) from about 0.5% to about 10% by weight of a buffering agent; and
• d) a pharmaceutically acceptable carrier.

Key elements and specifications within the claims include:

• NSAID Selection: The patent explicitly lists a range of NSAIDs, including ibuprofen (the most prominent example), naproxen, flurbiprofen, ketoprofen, suprofen, fenoprofen, diclofenac, and ketorolac. It also encompasses their pharmaceutically acceptable salts.
• Hydrophilic Polymer: The inclusion of a specific type of hydrophilic polymer is crucial. These polymers must have a molecular weight ranging from approximately 1,000 to 100,000 Daltons. Furthermore, their function is defined by their ability to swell in aqueous media and form a hydrogel. Examples of such polymers mentioned in the patent specification include hydroxypropyl cellulose, hydroxypropyl methylcellulose, and polyethylene oxide.
• Buffering Agent: The presence of a buffering agent is another critical component. The specified range is from about 0.5% to about 10% by weight. Buffering agents are intended to maintain a specific pH environment conducive to the dissolution of the NSAID. Examples provided in the patent include sodium citrate, potassium citrate, sodium acetate, and potassium acetate.
• Pharmaceutically Acceptable Carrier: This refers to standard components of oral dosage forms, such as diluents, binders, disintegrants, lubricants, and colorants, that are suitable for administration to humans.

Dependent claims further specify:

• The NSAID being ibuprofen (Claim 2).
• The hydrophilic polymer being hydroxypropyl cellulose (Claim 3).
• The hydrophilic polymer being hydroxypropyl methylcellulose (Claim 4).
• The hydrophilic polymer having a molecular weight from about 5,000 to about 50,000 (Claim 5).
• The buffering agent being an alkali metal citrate (Claim 6).
• The buffering agent being sodium citrate (Claim 7).
• The dosage form being a tablet (Claim 8).
• The dosage form containing a disintegrant (Claim 9).
• The dosage form having a compressed tablet core coated with a film coating (Claim 10).

These dependent claims delineate specific compositions and configurations that fall under the broader protection of Claim 1.

What is the Scope of Protection Offered by the Patent?

The scope of U.S. Patent 5,508,020 is defined by its claims. It protects the specific combination of an NSAID (from a defined list), a particular type of hydrophilic polymer, and a buffering agent within an oral dosage form. The patent is not limited to ibuprofen but extends to other listed NSAIDs and their salts. The critical aspect is the functionality of the hydrophilic polymer (swelling to form a hydrogel) and its molecular weight range.

The scope aims to cover formulations that exhibit enhanced dissolution and absorption characteristics, leading to faster pain relief. This means any oral dosage form containing an NSAID from the specified list, combined with a hydrophilic polymer meeting the molecular weight and swelling criteria, and a buffering agent within the stated percentages, would likely infringe the patent if manufactured or sold in the U.S. during its term.

The patent's disclosure also provides a basis for potential future improvements or variations that may fall under its scope through the doctrine of equivalents, depending on specific infringing products.

What is the Status and Term of U.S. Patent 5,508,020?

U.S. Patent 5,508,020 was granted on April 11, 1996. As a utility patent, its term is generally 20 years from the filing date, subject to maintenance fees.

• Filing Date: September 28, 1994
• Grant Date: April 11, 1996
• Expiration Date: September 28, 2014 (20 years from the filing date)

Therefore, U.S. Patent 5,508,020 is expired and no longer provides active patent protection.

What is the Patent Landscape Surrounding U.S. Patent 5,508,020?

The patent landscape for enhanced-absorption NSAID formulations is competitive and has evolved significantly since the expiration of U.S. Patent 5,508,020. Many companies have developed and patented various technologies aimed at improving the speed of onset and efficacy of NSAIDs.

Key areas of innovation in the NSAID formulation patent landscape include:

• Different Excipient Combinations: While U.S. Patent 5,508,020 focused on specific hydrophilic polymers and buffering agents, subsequent patents explore other classes of excipients or novel combinations to achieve rapid dissolution and absorption. This includes the use of specific disintegrants, surfactants, solid dispersions, or nano-milling techniques.
• Alternative NSAIDs: Patents may cover rapid-release formulations of NSAIDs other than those listed in U.S. Patent 5,508,020, or combinations of NSAIDs with other active ingredients.
• Specific Dosage Forms and Manufacturing Processes: Innovations in tablet coatings, tablet structures (e.g., bilayer tablets), granulation methods, or continuous manufacturing processes can also be patented if they offer advantages in terms of dissolution, stability, or patient compliance.
• Combinations with Other Active Ingredients: Formulations combining NSAIDs with other therapeutic agents (e.g., proton pump inhibitors for gastroprotection, or other analgesics) are also a significant area of patenting.

Examples of related patenting areas (note: these are general categories, not specific patent numbers infringing or being infringed by 5,508,020):

• Rapidly Disintegrating Tablets: Patents covering formulations that disintegrate rapidly in the oral cavity or stomach, often employing specific superdisintegrants.
• Solid Dispersion Technologies: Patents utilizing techniques to disperse the NSAID in an amorphous state within a polymer matrix to enhance solubility.
• Nano- and Micro-particle Formulations: Patents focusing on reducing particle size of the NSAID to increase surface area and improve dissolution.
• Gastroretentive Formulations: While not directly related to rapid release, patents in this area aim to prolong the residence time of NSAIDs in the stomach, potentially influencing absorption profiles.

Impact of Expiration:

The expiration of U.S. Patent 5,508,020 on September 28, 2014, means that the specific technology it protected is now in the public domain. This allows generic manufacturers and other pharmaceutical companies to develop and market oral formulations that incorporate the elements described in its claims without fear of direct patent infringement from this specific patent. However, these generic formulations must still navigate any other active patents that may exist for improvements, different excipients, or specific manufacturing processes used in their product.

The Procter & Gamble Company, and subsequent rights holders, would have likely leveraged this patent to establish market exclusivity for products based on its claims. Upon expiration, competition from generic versions of such enhanced-release ibuprofen formulations would have increased.

How Does U.S. Patent 5,508,020 Relate to Over-the-Counter (OTC) Ibuprofen Products?

U.S. Patent 5,508,020 specifically aimed to improve the speed of onset of analgesic effect and absorption of NSAIDs, primarily ibuprofen, in oral dosage forms. This directly relates to the development of OTC ibuprofen products that offer faster pain relief compared to standard formulations.

Products marketed with claims of "rapid relief" or "fast-acting" may have historically been based on technologies protected by this patent or similar proprietary innovations. The patent enabled The Procter & Gamble Company to differentiate its ibuprofen products in the competitive OTC market by offering a perceived performance advantage.

With the expiration of the patent, other manufacturers can now produce and market ibuprofen formulations that utilize the same combination of NSAID, hydrophilic polymer, and buffering agent as described in the expired patent. This would likely lead to increased availability of fast-acting OTC ibuprofen options from multiple brands.

However, it is important to note that the market for OTC ibuprofen is highly competitive. Many companies have invested in their own R&D to develop proprietary technologies for enhanced NSAID delivery. Therefore, while the specific claims of 5,508,020 are no longer protected, other patents covering different excipients, processing methods, or specific performance characteristics of fast-acting ibuprofen formulations may still be in force.

Key Takeaways

• U.S. Patent 5,508,020 protected oral formulations of NSAIDs, notably ibuprofen, utilizing specific hydrophilic polymers (1,000-100,000 Da, hydrogel-forming) and buffering agents (0.5-10% by weight) to enhance dissolution and absorption.
• The patent expired on September 28, 2014.
• The expiration has made the core technology described in the patent available for use by generic manufacturers and other pharmaceutical companies.
• The patent landscape for fast-acting NSAID formulations remains active, with ongoing innovation in excipient combinations, particle size reduction, and alternative delivery systems.
• The patent was instrumental in enabling The Procter & Gamble Company to offer differentiated, fast-acting OTC ibuprofen products during its term.

Frequently Asked Questions

1. Can I legally manufacture an ibuprofen tablet using a 15,000 Da hydroxypropyl cellulose and sodium citrate buffer now that U.S. Patent 5,508,020 has expired? Yes, the specific formulation elements described in U.S. Patent 5,508,020 are now in the public domain due to patent expiration, permitting their use in manufacturing. However, ensure no other active patents cover your specific formulation or manufacturing process.
2. Does U.S. Patent 5,508,020 cover all fast-acting ibuprofen formulations on the market today? No, U.S. Patent 5,508,020 expired in 2014. While it covered a specific approach to fast-acting formulations, many other patents exist that protect different technologies for achieving rapid NSAID release and absorption.
3. What specific NSAIDs were protected by U.S. Patent 5,508,020, beyond ibuprofen? The patent also covered naproxen, flurbiprofen, ketoprofen, suprofen, fenoprofen, diclofenac, ketorolac, and their pharmaceutically acceptable salts.
4. Were there any specific molecular weight ranges for the hydrophilic polymers mentioned in the patent? Yes, the patent specified a molecular weight range of from about 1,000 to about 100,000 Daltons for the hydrophilic polymers.
5. What was the primary benefit that formulations protected by U.S. Patent 5,508,020 aimed to provide to patients? The primary benefit targeted was rapid pain relief, achieved through improved oral absorption and a faster onset of the analgesic effect compared to conventional NSAID formulations.

Citations

[1] The Procter & Gamble Company. (1996). U.S. Patent 5,508,020 A: Oral Formulations of Certain Non-Steroidal Anti-inflammatory Drugs. United States Patent Office.

Drugs Protected by US Patent 5,508,020

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 5,508,020

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	152918
Austria	222264
Australia	4528793
Australia	5402694
Australia	688264
Australia	696206