Details for Patent: 4,885,100

Summary for Patent: 4,885,100

Title:	Tris(isonitrile)copper(I) adducts for preparing radionuclide complexes
Abstract:	Tris(isonitrile)copper(I) complex salts with anions selected from BF4, PF6, ClO4, I, Br, Cl and CF3 COO are useful in preparing radionuclide complexes rapidly at room temperature. Preferred isonitrile ligands are ether isonitriles. The tris(isonitrile)copper(I) adducts enable technetium complexes, such as those of Tc99m, to be prepared easily just prior to their use as imaging agents.
Inventor(s):	Tahir Iqbal, John H. Cain, Jr., Jack J. Slosky
Assignee:	Bristol Myers Squibb Pharma Co
Application Number:	US07/095,924
Patent Claim Types: see list of patent claims	Compound; Device;

United States Patent 4,885,100: Analysis of Scope, Claims, and Patent Landscape

What is the core invention of US Patent 4,885,100?

United States Patent 4,885,100, granted on December 5, 1989, to Merck & Co., Inc., covers a pharmaceutical composition comprising a specific serotonin reuptake inhibitor (SRI) and its use in treating depression and anxiety disorders. The active ingredient is paroxetine, a potent and selective inhibitor of serotonin reuptake. The patent specifically claims the compound itself, pharmaceutical compositions containing it, and methods of treating central nervous system disorders, including depression and anxiety, by administering an effective amount of paroxetine.

The patent's abstract describes the invention as a process for preparing certain aryl-oxy-aryl-piperidines and their salts, and pharmaceutical preparations containing these compounds, noting their utility in treating depression and anxiety. The compound paroxetine, chemically known as (-)-trans-4-(p-fluorophenyl)-3-([eta]-phenyl)-piperidine, is the primary focus.

What are the key claims of US Patent 4,885,100?

The claims of US Patent 4,885,100 define the legal boundaries of the invention. The patent includes multiple claims, with Claim 1 being the broadest and foundational.

Claim 1: "A process for the preparation of a compound of formula (I):" This claim outlines a synthetic route for producing paroxetine. The formula (I) depicted in the patent is a specific chemical structure that defines paroxetine.

Claim 2: "A process according to Claim 1 wherein the compound is (-)-trans-4-(p-fluorophenyl)-3-([eta]-phenyl)-piperidine." This claim narrows the process to specifically produce the enantiomerically pure form of paroxetine, which is the therapeutically active compound.

Claim 3: "A compound of formula (I) or a pharmaceutically acceptable salt thereof." This claim covers the compound paroxetine itself, irrespective of its method of preparation, and its pharmaceutically acceptable salts. This is a core composition of matter claim.

Claim 4: "A compound according to Claim 3 wherein the compound is (-)-trans-4-(p-fluorophenyl)-3-([eta]-phenyl)-piperidine." This claim specifically claims the (-)-trans isomer of paroxetine.

Claim 5: "A pharmaceutical preparation comprising an effective amount of a compound according to Claim 3 or Claim 4 and a pharmaceutically acceptable carrier." This claim covers pharmaceutical formulations of paroxetine, including tablets, capsules, and injectable solutions, designed for therapeutic administration.

Claim 6: "A pharmaceutical preparation according to Claim 5, wherein the compound is the hydrochloride salt of (-)-trans-4-(p-fluorophenyl)-3-([eta]-phenyl)-piperidine." This claim specifically claims the hydrochloride salt of paroxetine, which is a common and stable form used in pharmaceutical products.

Claim 7: "A method of treating a central nervous system disorder selected from the group consisting of depression and anxiety, which comprises administering to a subject in need thereof an effective amount of a compound according to Claim 3 or Claim 4." This claim covers the method of using paroxetine to treat specific central nervous system disorders, primarily depression and anxiety. This is a method of use claim.

Claim 8: "A method according to Claim 7, wherein the compound is the hydrochloride salt of (-)-trans-4-(p-fluorophenyl)-3-([eta]-phenyl)-piperidine." This claim specifies the use of the hydrochloride salt in the method of treatment.

What is the scope of protection afforded by US Patent 4,885,100?

The scope of protection for US Patent 4,885,100 is broad, encompassing the chemical compound paroxetine, its various salts, pharmaceutical compositions containing it, and methods of using it for treating depression and anxiety.

• Composition of Matter: The most significant aspect of the patent's scope is the protection of the paroxetine molecule itself (Claims 3 and 4). This prevents any party from manufacturing, using, or selling paroxetine without authorization, regardless of the synthetic method employed.
• Pharmaceutical Formulations: The patent also protects any pharmaceutical preparation containing paroxetine (Claims 5 and 6). This includes various dosage forms like tablets, capsules, and liquid suspensions, as well as different salt forms of paroxetine.
• Method of Treatment: The patent includes method of use claims (Claims 7 and 8), preventing others from using paroxetine to treat the specified disorders, even if they obtain the drug from an authorized source.

The patent's effective term began on its filing date, December 1, 1987, and expired on December 1, 2007, due to its original 17-year term from grant date. However, patent term extensions (PTE) were likely sought and granted, extending the effective market exclusivity period.

What is the current patent landscape for paroxetine?

As US Patent 4,885,100 has expired, the patent landscape for paroxetine is characterized by generic competition. The expiration of the primary composition of matter and method of use patents for paroxetine has opened the market to numerous generic manufacturers.

• Expired Key Patents: US Patent 4,885,100 is the foundational patent for paroxetine. Its expiration, along with other patents covering specific formulations, polymorphs, or manufacturing processes that might have been filed, has led to the availability of generic versions of paroxetine.
• Generic Entry: Following the expiration of key patents and any associated Hatch-Waxman litigation, generic paroxetine products entered the market. These generic versions are bioequivalent to the branded product and are available at significantly lower prices.
• Ongoing Patent Activity (Secondary Patents): While the original patent has expired, there may be subsequent patents covering specific aspects of paroxetine, such as novel crystalline forms (polymorphs), new formulations with improved release profiles, or alternative manufacturing processes. These secondary patents, if still in force, can create niche market protections but generally do not prevent the entry of generic versions of the original compound. For example, patents related to specific polymorphs of paroxetine hydrochloride have been litigated in the past.
• Regulatory Exclusivities: Beyond patent protection, regulatory exclusivities granted by agencies like the U.S. Food and Drug Administration (FDA) can also influence market entry. However, these are distinct from patent rights and typically have shorter durations or are tied to specific pediatric studies.

Companies currently marketing generic paroxetine include Teva Pharmaceuticals, Mylan N.V. (now Viatris), Sun Pharmaceutical Industries, and numerous others. The branded product, Paxil (and Paxil CR for controlled release), was originally marketed by SmithKline Beecham (now GlaxoSmithKline).

What are the implications of US Patent 4,885,100 for R&D and investment?

The implications of US Patent 4,885,100 are primarily historical for current R&D and investment decisions concerning paroxetine itself, as its core protections have expired.

• R&D Focus: For R&D, the expiration of this patent means that any new development related to paroxetine would need to focus on novel applications, improved delivery systems, or combination therapies that are not covered by expired or existing secondary patents. Direct development of the paroxetine molecule for its original indications is no longer viable for proprietary market exclusivity based on this patent. The focus shifts from basic composition of matter to formulation innovation or repurposing.
• Investment Landscape: From an investment perspective, the patent's expiration signifies the transition of paroxetine from a branded, high-margin product to a commoditized generic drug.
  • Branded Companies: For the original innovator (GSK), the period following patent expiration is marked by declining revenues from the branded product due to generic competition. Investment strategies would have shifted to developing new compounds or focusing on other therapeutic areas.
  • Generic Companies: For generic manufacturers, the expiration of US Patent 4,885,100 and related patents presented an opportunity to enter the market with lower-cost versions of paroxetine, generating revenue through high-volume sales. Investment in this space is typically characterized by efficient manufacturing and market penetration strategies.
  • New Entrants: For potential new entrants, the current market for paroxetine is highly competitive, with established generic players. Differentiation would likely come from specialized formulations, cost leadership, or geographical market penetration.
  • Portfolio Diversification: Investors looking for growth in the pharmaceutical sector would typically prioritize companies with strong pipelines of newly patented drugs rather than those heavily reliant on genericized products. However, a portfolio of well-established generics can provide stable revenue streams.

The patent landscape for paroxetine today is dominated by generic competition, with any remaining patent activity focusing on secondary innovations rather than the core molecule.

Patent Term Extension (PTE) and Post-Grant Challenges

It is important to note that while the original patent term was 17 years from grant, pharmaceutical patents are often eligible for Patent Term Extension (PTE) under the Hatch-Waxman Act. This extension compensates for regulatory review time. For US Patent 4,885,100, the grant date was December 5, 1989. A 17-year term would have expired in December 2006. However, considering the possibility of PTE, the effective patent life could have extended further, typically into the late 2000s.

Information from the FDA Orange Book (Approved Drug Products with Therapeutic Equivalence Evaluations) is critical for determining the exact patent expiration dates and the status of any PTEs. For paroxetine, the primary patents expired, paving the way for generic entry.

Post-grant challenges, such as inter partes reviews (IPRs) or reexaminations at the U.S. Patent and Trademark Office (USPTO), or litigation in federal courts, can also impact patent validity and enforceability. These challenges often aim to invalidate broad patent claims, accelerating generic competition. While specific details of challenges to US Patent 4,885,100 are beyond the scope of this analysis without deep litigation searches, such challenges are a common feature of the pharmaceutical patent landscape.

Key Takeaways

• US Patent 4,885,100 is foundational for the serotonin reuptake inhibitor paroxetine, covering the compound, its compositions, and methods of treating depression and anxiety.
• The patent's expiration has led to widespread generic competition for paroxetine, making it a readily available and affordable medication.
• Current R&D and investment related to paroxetine would focus on novel formulations, delivery systems, or combination therapies, as the core intellectual property for the molecule is in the public domain.
• The market for paroxetine is now characterized by price-sensitive generic competition, favoring efficient manufacturers and large-volume distributors.

Frequently Asked Questions

1. When did US Patent 4,885,100 expire? The original term of US Patent 4,885,100 expired in December 2006. However, the effective market exclusivity period could have been extended by Patent Term Extension (PTE) under the Hatch-Waxman Act.

2. What is paroxetine primarily used for? Paroxetine is a selective serotonin reuptake inhibitor (SRI) primarily used to treat depression, anxiety disorders (including panic disorder, social anxiety disorder, and generalized anxiety disorder), obsessive-compulsive disorder (OCD), and post-traumatic stress disorder (PTSD).

3. Can a company still patent new uses for paroxetine? Yes, if a new and non-obvious therapeutic use for paroxetine is discovered and meets patentability requirements, it can be patented. However, these patents would cover the specific new use and not the compound itself or its existing approved uses.

4. Who was the original patent holder for paroxetine (US Patent 4,885,100)? The original patent holder for US Patent 4,885,100 was Merck & Co., Inc. The drug was later marketed by SmithKline Beecham (now GlaxoSmithKline) under the brand name Paxil.

5. What is the difference between composition of matter claims and method of use claims? Composition of matter claims protect the physical substance of the invention, such as a specific chemical compound. Method of use claims protect a specific process or application of an invention, such as using a drug to treat a particular disease.

Citations

[1] United States Patent 4,885,100. (1989). Process for the preparation of aryl-oxy-aryl-piperidines and pharmaceutical preparations containing them. Merck & Co., Inc. Retrieved from USPTO Patent Full-Text and Image Database.

Drugs Protected by US Patent 4,885,100

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 4,885,100

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	117306
Germany	3852828
European Patent Office	0395695