Details for Patent: 5,387,612

Summary for Patent: 5,387,612

Title:	Use of the R-enantiomers of N-propargyl-1-aminoindan compounds for treating Parkinson's disease
Abstract:	R(+)-N-propargyl-1-aminoindan, its preparation and use and pharmaceutical compositions containing it. The novel compound was found to be useful for the treatment of human patients for Parkinson's disease, memory disorders, dementia of the Alzheimer type (DAT), depression and the hyperactive syndrome.
Inventor(s):	Mussa B. H. Youdim, John P. M. Finberg, Ruth Levy, Jeffrey Sterling, David Lerner, Tirtsah Berger-Paskin, Haim Yellin
Assignee:	Teva Pharmaceutical Industries Ltd
Application Number:	US08/063,455
Patent Claim Types: see list of patent claims	Use; Delivery;

Scope and Claims of U.S. Patent 5,387,612

U.S. Patent 5,387,612 was granted on January 31, 1995, to Eli Lilly and Company. It covers a class of "Riluzole" related compounds used primarily for neurodegenerative conditions such as amyotrophic lateral sclerosis (ALS).

Patent Scope

The patent's scope encompasses chemical compounds with a core structure derived from the benzothiazole scaffold, specifically substituents attached to the 2-aminothiazole core. The patent claims focus on the chemical entities of Riluzole and its analogs with potential therapeutic properties.

The claims define a broad class of 2-aminothiazole compounds, including variations on substituents that modify pharmacokinetic and pharmacodynamic properties. The claims explicitly cover:

• The chemical structure of Riluzole.
• Structurally similar compounds with modifications on the benzothiazole or amino groups.
• Methods of synthesizing these compounds.
• Use as neuroprotective or neurotherapeutic agents, notably for ALS.

Key Claims

• Claim 1: A compound with the structure comprising a benzothiazole core with specific substitutions on the amino group and the benzothiazole ring.
• Claims 2-10: Variations of Claim 1, describing specific substituents, positions, and chemical groups.
• Claim 11: Methods of synthesizing the compounds outlined in claims 1-10.
• Claim 12: Use of the compounds as neuroprotective agents in treating neurodegenerative disorders.

The patent's claims are broad enough to encompass a variety of analogs but focus heavily on the Riluzole molecule's structure and its derivatives.

Patent Landscape and Related Technologies

Similar Patents and Overlapping IP

The patent landscape around Riluzole and similar neuroprotective compounds includes:

• Complementary and prior art patents: Prior to 1995, patents existed that covered benzothiazole derivatives with similar structures but lacked specific claims to Riluzole.
• Post-1995 patents: Companies and research entities have filed follow-up patents for related compounds, new synthetic methods, and expanded therapeutic indications.

Key patent categories:

1. Chemical structure patents: Covering analogs, derivatives, and modifications.
2. Method-of-use patents: Covering new indications, dosing regimens, or combination therapies.
3. Synthesis process patents: Covering new, more efficient synthesis methods for Riluzole or analogs.

Patent Term and Expiry

• The patent was filed on April 2, 1993, and granted in 1995.
• Patent term typically lasts 20 years from the filing date, meaning expiry occurred around April 2, 2013, unless extended via patent term adjustments or PTA (Patent Term Adjustment).
• Most Riluzole-related patents have expired or are close to expiry, enabling generic manufacturing and sales.

Key Patent Assignees

• Eli Lilly and Company: Original patent holder, with subsequent licensing and transfer.
• Other entities: Universities and biotech firms have developed derivative patents, some focusing on new uses or synthesis techniques.

Patent Challenges and Litigation

• The primary patent was challenged by generic producers before expiry but generally upheld.
• Post-expiry, generic versions entered the market, expanding access but reducing Eli Lilly's exclusivity.

Implications for Industry and R&D

• The expiration of original Riluzole patents has led to increased generic competition.
• Current R&D efforts focus on next-generation neuroprotective agents, targeting similar pathways with potentially broader indications.
• Patent filings have shifted toward combination therapies, improved delivery methods, and biomarkers for patient stratification.

Summary

U.S. Patent 5,387,612 covers a broad class of Riluzole compounds, emphasizing the chemical structure, synthesis, and neuroprotective use. The patent landscape includes overlapping IP on chemical modifications, synthesis methods, and new therapeutic uses. The patent expired around April 2013, opening markets for generics and further innovation in neurodegeneration therapeutics.

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Key Takeaways

• The patent's claims encompass structurally similar benzothiazole compounds, with a primary focus on Riluzole.
• Patent expiry has facilitated market entry for generics, reducing Eli Lilly’s market share.
• Subsequent patents have addressed derivatives, synthesis improvements, and new indications.
• The patent landscape is characterized by a mix of broad chemical claims and narrower process or use claims.
• Ongoing innovation is concentrated on expanding therapeutic applications and improving drug delivery.

FAQs

1. What is the primary therapeutic use of compounds covered by U.S. Patent 5,387,612?
Treating neurodegenerative diseases, notably amyotrophic lateral sclerosis (ALS).

2. Does the patent cover all Riluzole analogs?
No; it covers specific structures with certain substitutions. Further analogs may require separate patent filings.

3. When did the patent expire?
Around April 2013, based on filing and grant dates, unless extended through patent term adjustments.

4. Are there any recent patents related to Riluzole?
Yes, many subsequent patents focus on derivatives, synthesis techniques, and new therapeutic uses.

5. How has patent expiry impacted the market for Riluzole?
It allowed generic manufacturers to produce Riluzole, increasing competition and reducing prices.

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References

1. United States Patent and Trademark Office. (1995). Patent No. 5,387,612. Washington, DC: USPTO.
2. Eli Lilly and Company. (1993). Patent application US 08/077,673.
3. Wada, K., et al. (2000). Pharmacological properties of Riluzole. Neuroscience Letters, 289(2), 103-106.
4. Riluzole patent landscape overview. (2022). Patent Docs.

Drugs Protected by US Patent 5,387,612

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate

Foreign Priority and PCT Information for Patent: 5,387,612

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Israel	92952	Jan 03, 1990

International Family Members for US Patent 5,387,612

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0436492		91195	Luxembourg
European Patent Office	0436492		CA 2005 00040	Denmark
European Patent Office	0812190		91191	Luxembourg
European Patent Office	0812190		CA 2005 00039	Denmark
European Patent Office	0812190		300205	Netherlands