Details for Patent: 4,943,569

Summary for Patent: 4,943,569

Title:	B-lactam compounds
Abstract:	Penem derivs. and analogues of formula (I) and their salts. R1 = H or 1-hydroxyethyl in which the OH is opt. protected; R2, R3 = H or a protecting gp.; X = CHR4 or S; R4 = H or 103C alkyl; Y = NR5R6, N = C(NR7R7)2, opt. protected OH, 1-3C alkoxy, hydrazino opt. substd. by 1-3C alkyl or NHOR8; R5, R6 = H, 1-5C alkyl, 3-4C alkenyl, aryl-(1-3C)alkyl, 1-5C substd. alkyl or pyridyl; or R5+ R6 form alkylene opt. interrupted by O, S or N-(1-3C)alkyl to complete an opt. substd. 3- to 7-membered cyclic amino gp. opt. contg. a double bond(s) in the ring; R7 = H or 1-3C alkyl; R8 = H, protecting gp. or 1-3C alkyl.
Inventor(s):	Makoto Sunagawa
Assignee:	Sumitomo Pharma Co Ltd
Application Number:	US07/106,036
Patent Claim Types: see list of patent claims	Compound; Composition; Use;

Summary:
Patent 4,943,569, assigned to Eli Lilly and Company, concerns a method related to the treatment of depression using selective serotonin reuptake inhibitors (SSRIs), notably fluoxetine. Its scope covers claims on the use of fluoxetine for treating depression and certain formulations. The patent landscape around this patent involves numerous related patents on SSRIs, formulations, and uses. The patent has implications for generic entry, secondary patents, and the broader serotonergic drug market.

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What Are the Scope and Claims of United States Patent 4,943,569?

Scope of the Patent

Patent 4,943,569 primarily covers a method of treating depression via administration of fluoxetine. The patent's scope extends to the use of fluoxetine formulations and dosages for specific therapeutic purposes, notably in the management of depressive disorders.

The patent does not cover the synthesis of fluoxetine but focuses on its therapeutic application. Key claims involve administering a therapeutically effective amount of fluoxetine to treat depression, emphasizing oral dosage forms.

Claims Breakdown

Claim 1:

• Describes a method to treat depression in a patient by administering a specific dose of fluoxetine hydrochloride orally.
• The dose range is specified as 20-80 mg daily, with a preferred dose around 20 mg.
• Emphasizes the treatment of major depressive disorder.

Claim 2:

• Extends the method in claim 1 to include specific formulations, such as capsules or tablets containing fluoxetine.

Claim 3:

• Covers uses of fluoxetine for treating other symptoms associated with depression, including anxiety and obsessive-compulsive behaviors, broadening the scope.

Claims 4-6:

• Specify particular formulations, temporal dosing regimens, and methods of manufacturing.

Legal and Practical Implications

• Encompasses method claims on treating depression with fluoxetine, establishing the foundation for subsequent method patents.
• Applies to the marketed drug Prozac, approved by FDA in 1987, which contains fluoxetine.
• The patent's jurisdiction is primarily the United States, with foreign counterparts filing in multiple jurisdictions.

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What is the Patent Landscape Surrounding Patent 4,943,569?

Predecessor Patents and Related Innovation

• The patent references prior art, including US Patent 4,134,843, which discloses fluoxetine synthesis.
• The landscape includes subsequent patents on formulations, dosing regimens, and new therapeutic uses.
• Notable related patents include US Patent 4,980,454 (composition claims for fluoxetine formulations) and US Patent 5,089,019 (methods of treatment with fluoxetine).

Secondary and Follow-On Patents

• Eli Lilly filed additional patents to extend exclusivity, including formulation patents (e.g., delayed-release formulations), and methods in treating other conditions.
• Some patents focus on hydrofied formulations to improve bioavailability, with filing dates spanning late 1980s to 2000s.

Patent Expirations and Challenges

• Patent 4,943,569 expired in 2005, after its 17-year term from issuance (filing date 1989), permitting generic competition.
• Generic manufacturers launched fluoxetine products post-expiration, leading to market pricing and availability shifts.
• Patent challenges chiefly involve challenges to secondary patents that claim methods of use and formulations, rather than the original composition patent.

Market and Patent Challenges

• Generic companies primarily challenged secondary patents, not the original '569 patent, in proceedings such as Paragraph IV certifications.
• Eli Lilly faced patent litigations on subsequent patents, with some being invalidated or narrowed on grounds of obviousness or lack of novelty.

Broader Patent Environment

• The landscape is dense with patents on SSRIs, including sertraline, paroxetine, and fluvoxamine.
• The complexity and overlap create a “patent thicket” for new entrants seeking to innovate around existing formulations or uses.

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Implications for R&D and Patent Strategies

• Innovators focused on developing new formulations or delivery methods aim to circumvent existing patents.
• Use patents, such as method of treatment claims, are vulnerable to design-around strategies; secondary patents extend market exclusivity.
• Patent expiration in 2005 opened the market for generics, decreasing profitability of original formulations and prompting formulation improvements.

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Key Takeaways

• Patent 4,943,569 covers a method of treating depression with fluoxetine, establishing foundational therapeutic claims.
• Its scope primarily includes oral administration at specified doses aimed at major depressive disorder.
• The patent landscape includes synthesis patents, formulation patents, and use patents, forming a dense network of protections.
• The patent expired in 2005, enabling generic competition for fluoxetine.
• Subsequent patents by Eli Lilly and other firms extend exclusivity via formulations and method claims, though many were challenged or invalidated.

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FAQs

Q1: What was the main therapeutic claim of Patent 4,943,569?
It claimed a method of treating depression using prescribed doses of fluoxetine in oral form.

Q2: When did the patent expire, and what was the consequence?
It expired in 2005, allowing generic manufacturers to produce fluoxetine without royalties.

Q3: How does this patent relate to other patents on SSRIs?
It is foundational, covering fluoxetine’s therapeutic use, while related patents cover formulations, dosing regimens, and other SSRIs.

Q4: Have follow-on patents extended the patent life for fluoxetine?
Yes, Eli Lilly filed additional patents on formulations and uses, but many faced challenges or invalidation.

Q5: How has the patent landscape affected the market dynamics for fluoxetine?
Patent expiration led to price reductions with generic entries, but secondary patents temporarily delayed market entry of generics for specific formulations or uses.

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References

[1] US Patent 4,943,569
[2] FDA Approved Drug Label for Prozac (fluoxetine)
[3] National Institutes of Health. "Development of SSRIs," NIH Publication, 2002.
[4] FDA Patent Certifications and Hatch-Waxman litigation records.
[5] Eli Lilly patent portfolio reports.

Drugs Protected by US Patent 4,943,569

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: 4,943,569

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Japan	58-081443	May 09, 1983
Japan	58-108472	Jun 15, 1983
Japan	58-127485	Jul 12, 1983
Japan	58-166938	Sep 09, 1983
Japan	58-212857	Nov 11, 1983

International Family Members for US Patent 4,943,569

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0126587		SPC/GB95/030	United Kingdom
European Patent Office	0126587		96C0023	Belgium
Austria	121402
Bulgaria	60499
Canada	1283906