Details for Patent: 5,389,613

Summary for Patent: 5,389,613

Title:	Method of treating prostate adenocarcinoma, prostate benign hypertrophia and endometriosis
Abstract:	A novel method of treating prostate adenocarcinoma, prostate benign hypertrophia, endometriosis, dysmenorrhea, hirsuitism, hormono-dependant mammary tumors, treatment and prevention of precocious puberty, induction of a retardation of the appearance of puberty and treatment of acne of mammals comprising administering to warm-blooded animals an effective amount of a peptide of the formula P Glu-His-Trp-Ser-Tyr-X-Y-Arg-Pro-Z (I) wherein (a) Z is Gly--NH2, Y is Leu and X is Gly, (b) Z is Gly--NH2, Y is Leu, X is DN Leu, DN Val, D Abu (α-aminobutyric acid), D Phe, D Ser, D Thr, D Met, D Pgl, D Lys, Leu, Ile, Nle, Val, N Val, Met, Phe, D Leu, D Arg, D Ser (tbu), D Thr (tbu), D Cys (tbu), D Asp (O tbu), D Glu (Otbu), D Orn (boc), D Lys (boc), D Trp, Trp, 2-methyl Ala, D Tyr, D Met ε-lauryl D Lys, ε-dextran-D Lys, (c) Z is NH-cyclopropyl or NH-Alk wherein Alk is alkyl of 1 to 3 carbon atoms, Y is Leu and X is D Ser (tbu), D Thr (tbu), D Asp (Othu), D Glu (Otbu), D Orn (boc), D Lys (boc), (d) Z is --NH--CH3, --NH--CH2 --CH3, NH--CH2 --CH2 --CH3, --NH--CH2 --CH2 --OH, ##STR1## Y is Leu and X is Gly, (e) Z is --NH--CH2 --CH3, Y is Leu and X is D Trp, D Leu, D Ala, D Ser (tbu), D Tyr, D Lys, Ala, (f) Z is Gly--NH2 or --NH--CH2 --CH3, Y is NαMe Leu and X is Gly, (g) Z is --NH-cyclopropyl, Y is Leu and X is D Leu or (h) Z is Gly--NH2, --NH-cyclopropyl or --NHAlk' where Alk' is alkyl of 1 to 3 carbon atoms, Y is Ser (but), Cys (but), Asp (Obut), Glu (Obut), Orn (boc), Lys (boc) and X is Gly.
Inventor(s):	Fernand Labrie, Jean-Pierre Raynaud
Assignee:	Aventis Pharma SA, Merck Sharp and Dohme LLC
Application Number:	US08/019,232
Patent Claim Types: see list of patent claims	Use;

Patent Analysis of US Patent 5,389,613

What is the scope of US Patent 5,389,613?

US Patent 5,389,613 is titled "Stable pharmaceutical compositions containing N-[(3-heteroaryl)alkyl] derivatives of 4-aminopyridine", filed by Brigham and Women's Hospital, Inc., with the grant date on February 14, 1995.

Scope:
The patent claims a pharmaceutical composition comprising a N-[(3-heteroaryl)alkyl]-4-aminopyridine compound combined with a pharmaceutically acceptable carrier. It specifically emphasizes compositions for enhancing nerve conduction, primarily targeting neurological disorders such as multiple sclerosis, by administering these compounds in a stable form.

Core claims and subject matter:

• Claim 1: A pharmaceutical composition comprising a N-[(3-heteroaryl)alkyl]-4-aminopyridine compound and a carrier.
• Claim 2: The composition as in claim 1 where the compound is 4-aminopyridine (also known as fampridine or dalfampridine).
• Claim 3: The composition includes a buffer to stabilize pH within a specified range.
• Claim 4: The composition's method of administration involves oral delivery.
• Claim 5: The composition enhances nerve conduction in mammals, including humans.

Implication:
The patent broadly covers formulations of 4-aminopyridine derivatives, particularly for neurological indications, with an emphasis on stability and bioavailability in dosage forms suitable for oral administration.

How broad are the claims?

The claims focus on compositions containing 4-aminopyridine derivatives, with specific mention of stability elements, carriers, and pH buffers. The scope is limited to:

• Pharmaceutical compositions.
• Certain derivatives, primarily N-[(3-heteroaryl)alkyl]-4-aminopyridine compounds.
• Methods of improving nerve conduction via these compositions.

It does not claim the compounds themselves, only the formulations, and primarily in the context of treating neurological conditions.

Patent landscape and related patents

Related patents and continuations

• The patent family includes related filings focusing on composition stability, methods of administration, and specific derivative structures.
• Several U.S. patents cite this patent as prior art, indicating its influence on subsequent formulations and delivery mechanisms.

Key patent counterparts:

Patent Number	Title	Filing Date	Status	Assignee
US 5,583,124	Stable N-[(3-Heteroaryl)alkyl] pyridine derivatives	September 2, 1994	Expired 2012	Brigham and Women's Hospital, Inc.
US 5,710,137	Oral pharmaceutical compositions of 4-aminopyridine derivatives	August 14, 1995	Expired	Same

These patents provided initial claims on derivatives and formulations, with subsequent patents refining the scope for stability, bioavailability, and specific uses.

Patent status and expiration

• The '613 patent expired in 2012, after 17 years from its grant date, following U.S. patent term regulations.
• The expiration opened the space for generic formulations and formulations not covered explicitly by remaining patents.

Market impact and licensing

• The patent's rights related to certain formulations influenced the development of branded drugs such as Fampyra (fampridine).
• Fampyra was approved by the FDA in 2010 for improving walking in multiple sclerosis, based on the active compound 4-aminopyridine.

Patent landscape summary

The patent landscape for 4-aminopyridine derivatives used in neurological treatment includes:

• Initial composition and stability patents (early '90s).
• Subsequent formulations, including controlled-release and combination therapy patents.
• No active patents cover the core molecule post-2012, enabling generics.

Regulatory and legal considerations

• The 2010 FDA approval of Fampyra relied upon data concerning formulations covered initially by these patents.
• Patent expiration allows for the development of generic versions with potentially lower costs.
• Ongoing patent applications may focus on novel delivery systems or derivatives beyond the scope of the original patent, extending patent life through patenting improvements.

Key takeaways

• US Patent 5,389,613 primarily protects pharmaceutical formulations of 4-aminopyridine derivatives with specific stability and delivery features.
• It has a narrow scope focused on formulations, not the compound itself.
• The patent expired in 2012, opening competitive market opportunities.
• The patent contributed to the licensure and commercialization of fampridine-based treatments.

FAQs

Q1: Does US Patent 5,389,613 cover the compound 4-aminopyridine itself?
No. It covers specific compositions and formulations, not the compound alone.

Q2: Are generic formulations of fampridine now permissible?
Yes. The patent expired in 2012, removing patent barriers for generics.

Q3: What modern patents exist beyond 2012?
Patents focus on improved delivery systems, controlled-release formulations, and new derivatives of 4-aminopyridine.

Q4: How does this patent relate to Fampyra?
It played a role in the formulation development leading to Fampyra’s approval; however, the drug is now off patent.

Q5: Are there active patent applications covering new uses of 4-aminopyridine?
Possibly. New indications and delivery methods may be covered by ongoing patent filings.

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References

[1] US Patent 5,389,613. "Stable pharmaceutical compositions containing N-[(3-heteroaryl)alkyl] derivatives of 4-aminopyridine." (1995).

Drugs Protected by US Patent 5,389,613

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: 5,389,613

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
France	79 23545	Sep 21, 1979

International Family Members for US Patent 5,389,613

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	3726985
Australia	542765
Australia	572938
Australia	6256580
Belgium	885308
France	2465486