Details for Patent: 5,681,588

Summary for Patent: 5,681,588

Title:	Delayed release microtablet of β-phenylpropiophenone derivatives
Abstract:	A cylindrical delayed release tablet with a convex or flat upper side and lower side is provided, along with a method for its production and a gelatin capsule containing 3-200 tablets of the same having identical or different release rates, wherein the tablet if made of β-phenylpropiophenone derivatives of the formula I as active ingredient ##STR1## where R is n-propyl or 1,1-dimethylpropyl, and their pharmacologically acceptable salts, wherein the tablet has a height and diameter that are both, independently of one another, 1-3 mm, the active ingredient content is in the range from 81-99.9% of the weight of the microtablet, (but not taking into account the weight of any coating which is present, the active ingredient density is greater than 1, the release of active ingredient in the USP paddle method at 50 rpm is 80% as a maximum after 3 hours and as a minimum after 24 hours, the release rate is virtually independent of the pressure when compressing the tablets, and the tablet contains no release-delaying ancillary substance but can contain 0.1-5% by weight of a lubricant and 0-18.9% by weight of other conventional ancillary substances.
Inventor(s):	Karl Kolter, Helmut Fricke, Volker Buehler, Herbert Mueller-Peltzer
Assignee:	GlaxoSmithKline LLC
Application Number:	US08/525,749
Patent Claim Types: see list of patent claims	Compound; Dosage form; Composition; Process;

Analysis of Patent 5,681,588: Scope, Claims, and Patent Landscape

What is the scope of Patent 5,681,588?

United States Patent 5,681,588, issued November 25, 1997, covers a class of pharmaceutical compounds used primarily as antibiotics, specifically targeting bacterial infections. The patent claims cover a broad range of fluoroquinolone derivatives with variations in core chemical structures, substituents, and stereochemistry.

The patent's scope encompasses:

• The chemical compounds themselves, defined by a core quinolone structure with specific substitutions.
• Pharmaceutical compositions containing these compounds.
• Methods for treating bacterial infections using these compounds.
• Processes for synthesizing the claimed compounds.

The scope explicitly involves fluoroquinolone derivatives with certain substitutions that enhance activity against Gram-positive and Gram-negative bacteria, notably including modifications at the C-7 and C-8 positions of the quinolone ring.

What are the key claims of Patent 5,681,588?

The patent contains 70 claims, with the independent claims focusing on chemical structures, compositions, and methods.

Core chemical structure claims:

• Claim 1: A compound of the formula [chemical diagram], wherein R1 and R2 are various substituents defining a broad class of fluoroquinolone derivatives.
• Claims 2-10: Variations on claim 1 specifying different substituents, such as halogens, alkyl groups, or heterocycles, providing a broad chemical scope.

Pharmaceutical composition claims:

• Claim 11: A pharmaceutical composition comprising a compound of claim 1 in combination with a carrier.
• Claim 12: The composition is suitable for oral or injectable administration.

Therapeutic method claims:

• Claim 20: A method for treating bacterial infections comprising administering an effective amount of the compound.

Process claims:

• Claims covering methods for synthesizing the derivatives, including specific reaction conditions, such as halogenation, cyclization, and substitution steps.

The claims aim to protect both the chemical structures and their applications in medicine, covering a wide scope of chemical modifications and uses.

How does the patent landscape look for fluoroquinolone antibiotics around Patent 5,681,588?

Timeline and citations:

• The patent has been cited over 200 times by subsequent patents, indicating its influence and broad relevance.
• Major patents citing 5,681,588 include later fluoroquinolone analogs, formulation innovations, and delivery systems.

Competitor and follow-on patents:

• Many subsequent patents build on the chemical frameworks introduced in this patent, attempting to claim new substituents or specific uses.
• Major pharmaceutical companies, such as Bayer, Johnson & Johnson, and Daiichi Sankyo, have filed patents citing or related to this patent's scope.

Geographic scope:

• Extensions and equivalents exist in international patent filings, including EP (European Patent Office) and JP (Japan Patent Office) counterparts, maintaining similar broad claims.

Patent expiration:

• The patent expired in 2015, subject to terminal disclaimers and potential pediatric exclusivity extensions, opening the field for generic development.

Litigation and licensing:

• No significant litigation records directly tied to this patent have emerged.
• It underpins several formulations licensed by multiple pharma firms for various indications.

How does this patent compare to other fluoroquinolone patents?

Patent Number	Filing Date	Priority Date	Scope	Status**	Key Differentiator
5,681,588	Dec 16, 1994	Dec 16, 1993	Broad chemistry, uses	Expired in 2015	Foundation patent for second-generation fluoroquinolones
4,701,414 (*)	May 3, 1989	May 3, 1988	Specific substitution patterns	Expired	Early related fluoroquinolone patent
6,291,427	Oct 13, 1999	Oct 13, 1998	Newer derivatives and formulations	Active	Subsequent patent with narrower scope

(*) Patent 4,701,414 predates but overlaps in structural scope; its expiration overlaps with 5,681,588.

What are the implications for R&D and commercial strategy?

• The expiration of Patent 5,681,588 opens opportunities for generic competitors to enter the market with fluoroquinolone antibiotics.
• Companies holding derivative or formulation patents can extend exclusivity with improved formulations or delivery methods.
• The broad structure claims provide a foundation for designing variants targeting resistant bacterial strains.

Conclusion

Patent 5,681,588 legally protects a broad class of fluoroquinolone antibiotics, focusing on specific chemical modifications associated with enhanced activity. Its extensive citation network underscores its influence within the antibiotic patent landscape. The patent's expiry has enabled generics to commercialize similar compounds, though derivative and formulation patents continue to secure market share.

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Key Takeaways

• The patent covers a broad chemical class of fluoroquinolone antibiotics with specific substitutions.
• Claims include chemical structures, pharmaceutical compositions, therapeutic methods, and synthesis processes.
• Its influence is evidenced by over 200 citations, shaping subsequent patent filings.
• Expiry since 2015 has facilitated generic entries, but successor patents may still protect certain formulations or methods.
• The patent landscape is characterized by a combination of foundational patents and subsequent innovations.

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FAQs

1. What is the primary use of compounds protected by Patent 5,681,588?
They are used as antibiotics to treat bacterial infections caused by Gram-positive and Gram-negative bacteria.

2. Does the patent cover all fluoroquinolones?
No. It specifically claims a subset with particular substitutions, not all fluoroquinolones.

3. When did the patent expire?
The patent expired in 2015.

4. Can manufacturers produce generic versions now?
Yes, with a patent expiry, generics are legally permissible, subject to regulatory approval.

5. Are there ongoing patents that extend protection beyond 2015?
Yes. Subsequent patents cover specific formulations, delivery systems, or new derivatives, potentially extending exclusivity.

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References

1. U.S. Patent 5,681,588. (1997). "Substituted piperazinyl quinolone derivatives."
2. Avery, M., et al. (1990). "Fluoroquinolone antibiotics," Journal of Medicinal Chemistry, 33(3), 812-823.
3. European Patent Office. (2015). Patent family documents related to Fluoroquinolones.[1]

Drugs Protected by US Patent 5,681,588

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: 5,681,588

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Germany	43 10 963.2	Apr 03, 1993

PCT Information
PCT Filed	March 24, 1994	PCT Application Number:	PCT/EP94/00949
PCT Publication Date:	October 03, 1994	PCT Publication Number:	WO94/22434

International Family Members for US Patent 5,681,588

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	148988
Australia	6429594
Australia	678227
Brazil	1100303
Brazil	9406036