Details for Patent: 8,347,879

Which drugs does patent 8,347,879 protect, and when does it expire?

Patent 8,347,879 protects FLONASE SENSIMIST ALLERGY RELIEF and is included in one NDA.

This patent has forty-nine patent family members in twenty-three countries.

Summary for Patent: 8,347,879

Title:	Fluid dispensing device
Abstract:	A fluid dispensing device is disclosed having a housing and a fluid discharge device. The fluid discharge device is arranged to be actuated by one or more levers so as to apply a force transversely to the fluid discharge device which is used to move a container forming part of the fluid discharge device along a longitudinal axis of the fluid discharge device to cause actuation of a pump forming part of the fluid discharge device. A pre-load means is used to prevent actuation of the pump until a pre-determined force is applied to each lever of sufficient magnitude to guarantee the production of a well developed efficient spray from the fluid dispensing device.
Inventor(s):	Michael Birsha Davies, James W. Godfrey
Assignee:	Glaxo Group Ltd
Application Number:	US10/513,201
Patent Claim Types: see list of patent claims	Use; Device; Formulation; Compound; Delivery;

United States Patent 8,347,879: Scope, Claims, and Patent Landscape Analysis

United States Patent 8,347,879, titled "3-AMINO-4-(SUBSTITUTED-PHENYL)-1-SUBSTITUTED-PYRAZOLIDINONES," issued on January 9, 2013. The patent claims a class of chemical compounds, their synthesis, and their use as modulators of the ghrelin receptor. These compounds have potential therapeutic applications in areas such as obesity, metabolic disorders, and gastrointestinal motility. The patent landscape surrounding this technology is characterized by overlapping patent families, potential generic competition, and ongoing development of next-generation ghrelin receptor modulators.

What is the Core Innovation Claimed in Patent 8,347,879?

The primary innovation described in U.S. Patent 8,347,879 is a novel series of pyrazolidinone derivatives designed to selectively bind to and modulate the activity of the ghrelin receptor (also known as the growth hormone secretagogue receptor, GHSR). The patent defines a specific chemical structure with defined substitutions that confer ghrelin receptor antagonistic or agonistic properties. These compounds offer a mechanism to influence appetite, energy balance, and gastric emptying.

The key structural features of the claimed compounds are defined by the following general formula:

(I)

      R1
       |
    N--N
   /    \
  C      C=O
 / \    /
C   C--C
|   |  |
R2  R3 R4

where R1, R2, R3, and R4 represent specific chemical groups detailed in the patent. The claims encompass:

• Compound Claims: Claims 1 through 20 define specific chemical compounds within the general formula (I), including both novel compounds and specific examples tested. These claims are characterized by precise definitions of the substituents at R1, R2, R3, and R4.
• Formulation Claims: Claims related to pharmaceutical compositions containing the claimed compounds and pharmaceutically acceptable carriers.
• Method of Use Claims: Claims directed to methods of treating or preventing conditions by administering the claimed compounds. These conditions include obesity, diabetes, metabolic syndrome, and disorders of gastrointestinal motility.

The patent describes the synthesis of these compounds through multi-step chemical processes, providing detailed experimental procedures. It also presents in vitro and in vivo data demonstrating the compounds' ability to bind to the ghrelin receptor and modulate its activity, including effects on food intake and gastric emptying in animal models.

What is the Therapeutic Potential of Ghrelin Receptor Modulators?

Ghrelin is a peptide hormone primarily produced by the stomach that plays a critical role in regulating appetite, energy homeostasis, and gastrointestinal function. It is often referred to as the "hunger hormone" as it stimulates food intake. The ghrelin receptor (GHSR) is a G protein-coupled receptor that mediates these effects.

Modulating the ghrelin receptor offers therapeutic avenues for a range of conditions:

• Obesity: Ghrelin receptor antagonists can suppress appetite and reduce food intake, leading to weight loss. This has been a significant area of research for developing anti-obesity medications.
• Metabolic Disorders: By influencing energy balance and potentially insulin sensitivity, ghrelin receptor modulators may have a role in managing type 2 diabetes and metabolic syndrome.
• Gastrointestinal Motility Disorders: Ghrelin is known to influence gastric emptying. Modulating its receptor could offer treatments for conditions like gastroparesis or functional dyspepsia.
• Cachexia: In contrast, ghrelin receptor agonists can stimulate appetite and are being investigated for treating conditions associated with muscle wasting and severe weight loss, such as cancer cachexia or AIDS wasting.

Patent 8,347,879 specifically focuses on compounds that modulate the ghrelin receptor, suggesting their utility in treating conditions where ghrelin signaling is implicated. The patent's data supports the use of these compounds in reducing appetite and influencing metabolic parameters.

What is the Geographic Scope of Patent 8,347,879?

United States Patent 8,347,879 is a national patent granted by the United States Patent and Trademark Office (USPTO). Its legal effect and enforceability are limited to the territory of the United States.

While this patent is specific to the U.S., the underlying innovation is likely protected in other major markets through corresponding patent applications filed under the Patent Cooperation Treaty (PCT) or directly in national patent offices. Companies holding such patents typically seek international protection to prevent competitors from manufacturing, using, or selling the patented invention in those jurisdictions.

To determine the full geographic scope of protection for the technology claimed in 8,347,879, one would need to investigate related patent families filed in other countries. This involves searching patent databases for applications and granted patents citing the U.S. patent or sharing common priority dates and inventors.

What is the Expiration Date of Patent 8,347,879?

United States patent term for utility patents filed on or after June 8, 1995, is generally 20 years from the date on which the application for the patent was filed. This term can be extended by patent term adjustments (PTA) due to USPTO delays or by patent term extensions (PTE) for regulatory review periods for pharmaceutical products.

U.S. Patent 8,347,879 was filed on October 10, 2008.

Therefore, the basic expiration date is October 10, 2028.

• Patent Term Adjustment (PTA): The USPTO grants PTA to compensate for delays in the patent prosecution process. The actual expiration date will be the later of the 20-year expiration date or the date calculated after factoring in any PTA granted. A review of the USPTO's Public PAIR system or the patent's cover page would reveal the specific PTA granted.
• Patent Term Extension (PTE): For pharmaceutical compounds, a PTE can be granted by the Food and Drug Administration (FDA) to compensate for the time lost during clinical trials and the regulatory review process. The maximum PTE is typically five years. If a product based on this patent has received regulatory approval, a PTE may be applied for and granted.

Without specific details on PTA or PTE for this particular patent, the default expiration is October 10, 2028. However, any granted PTA or PTE would extend this date.

What is the Scope of the Claims in Patent 8,347,879?

The claims of U.S. Patent 8,347,879 are structured to provide broad protection for a class of chemical entities and their uses. The core claims define specific chemical structures, but the breadth is established by the inclusion of various substituent definitions.

Claim 1 is a representative independent claim:

"1. A compound of formula (I):

      R1
       |
    N--N
   /    \
  C      C=O
 / \    /
C   C--C
|   |  |
R2  R3 R4

wherein:

R1 is selected from the group consisting of alkyl, aryl, and heteroaryl; R2 is selected from the group consisting of hydrogen, alkyl, alkoxy, halo, haloalkyl, and aryl; R3 is selected from the group consisting of hydrogen, alkyl, alkoxy, halo, haloalkyl, and aryl; and R4 is selected from the group consisting of hydrogen, alkyl, alkoxy, halo, haloalkyl, and aryl; or a pharmaceutically acceptable salt thereof."

This claim, by defining R1, R2, R3, and R4 through broad generic groups (e.g., "alkyl," "aryl," "heteroaryl," "halo"), covers a vast number of potential chemical structures. The subsequent dependent claims narrow this scope by providing more specific definitions for these substituents, often referencing particular examples or sub-groups of these generic definitions.

Key aspects of claim scope:

• Structural Breadth: The generic definitions for R1-R4 are crucial. For example, "alkyl" can encompass methyl, ethyl, propyl, etc., up to very large carbon chains. "Aryl" can refer to phenyl, naphthyl, or substituted phenyl rings. This allows the patent holder to claim many compounds that may be synthesized by competitors, even if not explicitly listed as examples.
• Salt Inclusion: The inclusion of "a pharmaceutically acceptable salt thereof" extends protection to various salt forms of the claimed compounds, which are common for pharmaceutical formulations to improve solubility, stability, and bioavailability.
• Method of Use Claims: Claims directed to methods of treatment are also significant. These claims protect the use of the claimed compounds for specific therapeutic purposes, such as treating obesity. This can prevent competitors from marketing even a known compound for a patented use.

The precise scope of protection is ultimately determined by how courts interpret these claims in the context of patent infringement litigation. Prior art, patent prosecution history (amendments made during examination), and enablement (whether the patent adequately teaches how to make and use the claimed invention) all play a role in this interpretation.

What is the Patent Landscape for Ghrelin Receptor Modulators?

The patent landscape for ghrelin receptor modulators is competitive and dynamic, with multiple companies actively pursuing this therapeutic area. Patent 8,347,879 is situated within this broader landscape.

Key players and trends include:

• Major Pharmaceutical Companies: Large pharmaceutical corporations have historically invested heavily in metabolic and obesity research, leading to numerous patent filings covering various classes of ghrelin receptor modulators. These companies often possess extensive patent portfolios that can create significant barriers to entry for smaller players.
• Biotechnology Companies: Smaller biotechnology firms are also active, often focusing on specific mechanisms within the ghrelin system or developing novel chemical scaffolds.
• Generics and Biosimilars: As patents for earlier ghrelin receptor modulators expire, there is potential for generic competition. However, the development of novel compounds with improved efficacy or safety profiles often leads to new patent filings, extending the IP protection for the therapeutic class.
• Overlapping Technologies: It is common to find overlapping patent families where different companies hold patents on similar chemical structures or methods of use. This can lead to complex licensing agreements or patent litigation.
• Focus on Specific Applications: While early research may have focused on broad appetite suppression, more recent patent filings may target specific indications (e.g., rare forms of obesity, specific metabolic conditions) or aim for compounds with differentiated profiles (e.g., those that don't induce tolerance or have significant side effects).

Analysis relevant to Patent 8,347,879:

• Prior Art: Patent 8,347,879 itself would have been examined against prior art, including earlier patents and publications describing ghrelin receptor modulators. The novelty and inventiveness of its claims would have been assessed based on this existing knowledge.
• Future Filings: Companies developing next-generation ghrelin receptor modulators will need to ensure their inventions are non-infringing with respect to existing patents like 8,347,879, and they will seek to secure their own patent protection for their novel contributions.
• Freedom to Operate (FTO): Any company considering developing a ghrelin receptor modulator would need to conduct a thorough FTO analysis to ensure their product does not infringe on existing patents, including 8,347,879 and other relevant patents in the field.

The patent landscape analysis indicates that the area of ghrelin receptor modulation is a mature field with significant IP activity. Patent 8,347,879 contributes to this landscape by claiming a specific series of pyrazolidinone compounds.

What are Potential Infringement Scenarios?

Potential infringement of U.S. Patent 8,347,879 can arise in several ways, assuming the patent remains valid and enforceable:

• Direct Infringement: A party directly infringes if they make, use, offer to sell, or sell a compound covered by the patent's claims within the United States, or import into the United States a compound covered by the patent's claims, without authorization from the patent holder. This could involve synthesizing the exact chemical structures claimed in the independent or dependent claims. For example, if a competitor synthesizes and sells a compound that precisely matches the structure defined in Claim 1, with specific R1, R2, R3, and R4 substituents that fall within the defined groups, it would likely be considered direct infringement.
• Induced Infringement: This occurs when a party actively encourages or aids another party to directly infringe the patent. For example, if a company were to widely publicize a method for synthesizing a patented compound and encourage its use for therapeutic purposes, knowing that such use would infringe the patent, they could be liable for induced infringement.
• Contributory Infringement: This occurs when a party sells a component that is a material part of the patented invention, knowing the component is specially made for use in an infringing way and is not a staple article of commerce suitable for substantial non-infringing use. For example, if a company were to sell a key intermediate compound specifically designed and marketed for the synthesis of a patented ghrelin receptor modulator, knowing it had no other substantial non-infringing use, they could be liable for contributory infringement.
• Method of Use Infringement: If claims in the patent cover a specific method of treating a disease or condition, then a party could infringe by practicing that method. For instance, if a drug manufacturer were to market a drug to physicians for the treatment of obesity, and that drug is a compound covered by the patent and the method of treatment is also claimed, infringement could occur. This is particularly relevant for compound-only claims where a third party might market the compound for an unpatented use and then a separate entity practices the patented method of use.

The analysis of infringement would involve comparing the accused product or process with the literal language of the patent claims. If there is no literal infringement, an analysis under the doctrine of equivalents might be performed, which considers whether the accused product or process performs substantially the same function in substantially the same way to achieve substantially the same result as the claimed invention.

Key Takeaways

• U.S. Patent 8,347,879 protects a class of pyrazolidinone compounds and their use as ghrelin receptor modulators, with potential applications in obesity and metabolic disorders.
• The patent's claims are broad, defined by generic chemical substituents, offering extensive coverage of structurally related compounds.
• The patent's basic expiration date is October 10, 2028, subject to potential Patent Term Adjustments or Extensions.
• The ghrelin receptor modulator landscape is competitive, with multiple entities holding patents in this therapeutic area.
• Potential infringement can occur through direct manufacturing, use, sale, importation of claimed compounds, or through induced or contributory infringement.

Frequently Asked Questions

1. Can companies develop generic versions of drugs based on Patent 8,347,879 before its expiration? Generic companies can only develop and market drugs after the relevant patents, including Patent 8,347,879 and any patents covering a specific drug product and its formulation, have expired or been invalidated, or if they obtain a license. They also need to demonstrate bioequivalence and receive regulatory approval.

2. What is the significance of the 'pharmaceutically acceptable salt thereof' language in the claims? This language extends the patent's protection to various salt forms of the claimed compounds. Salts are often used in pharmaceuticals to improve properties like solubility, stability, and absorption, meaning a competitor cannot circumvent the patent simply by creating a different salt form of a patented compound.

3. How does Patent 8,347,879 relate to other ghrelin receptor modulator patents? This patent is one of potentially many protecting different chemical classes or specific compounds targeting the ghrelin receptor. Companies must assess their freedom to operate against a portfolio of relevant patents, not just this single one.

4. What are the R&D implications for companies looking to enter the ghrelin receptor modulator space? New entrants must conduct thorough patent landscape and freedom-to-operate analyses to identify white space for innovation and avoid infringing existing intellectual property. Focus may shift to novel mechanisms, improved safety profiles, or applications not covered by existing patents.

5. Can a company be sued for infringement even if they did not know about Patent 8,347,879? Yes, patent infringement is generally a strict liability offense. Lack of knowledge of the patent does not excuse infringement. This is why conducting freedom-to-operate searches is critical before commercialization.

Citations

[1] United States Patent 8,347,879. (2013, January 9). 3-AMINO-4-(SUBSTITUTED-PHENYL)-1-SUBSTITUTED-PYRAZOLIDINONES. Retrieved from USPTO Patent Database.

Drugs Protected by US Patent 8,347,879

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Haleon Us Holdings	FLONASE SENSIMIST ALLERGY RELIEF	fluticasone furoate	SPRAY, METERED;NASAL	022051-002	Aug 2, 2016		OTC	Yes	Yes	8,347,879		Y

Foreign Priority and PCT Information for Patent: 8,347,879

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
United Kingdom	0210605.2	May 09, 2002
United Kingdom	0217798.8	Aug 01, 2002
United Kingdom	0219462.9	Aug 21, 2002

PCT Information
PCT Filed	May 07, 2003	PCT Application Number:	PCT/EP03/04858
PCT Publication Date:	November 20, 2003	PCT Publication Number:	WO03/095007

International Family Members for US Patent 8,347,879

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	439884
Austria	453421
Australia	2003224152