[Federal Register Volume 63, Number 201 (Monday, October 19, 1998)]
[Notices]
[Pages 55880-55882]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-27960]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Government-Owned Inventions; Availability for Licensing

AGENCY: National Institutes of Health, Public Health Service, DHHS.

ACTION: Notice.

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SUMMARY: The inventions listed below are owned by agencies of the U.S. 
Government and are available for licensing in the U.S. in accordance 
with 35 U.S.C. 207 to achieve expeditious commercialization of results 
of federally-funded research and development. Foreign patent 
applications are filed on selected inventions to extend market coverage 
for companies and may also be available for licensing.

ADDRESSES: Licensing information and copies of the U.S. issued patents 
and patent applications listed below may be obtained by contacting 
Carol Salata, Ph.D., at the Office of Technology Transfer, National 
Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville, 
Maryland 20852-3804; telephone: 301/496-7057 ext. 232; fax: 301/402-
0220; e-mail: [email protected]. A signed Confidential Disclosure 
agreement will be required to receive copies of the patent 
applications.

Dimeric Naphthylisoquinoline Alkaloids and Synthesis Methods 
Thereof

G Bringmann, S Harmsen, MR Boyd (NCI)
Serial No. 08/279,339 filed 22 Jul 94 (U.S. Patent 5,571,919 issued 05 
Nov 96) and Serial No. 08/674,359 filed 01 Jul 96 (U.S. Patent 
5,789,594 issued 04 Aug 98)

    This invention embodies the synthesis and novel compounds 
comprising homodimeric and heterodimeric napthylisoquinoline

[[Page 55881]]

alkaloids and derivatives. The methods presented in the invention are 
advantageous because they permit, for the first time, the in vitro 
synthesis of compounds for which the only known natural source is the 
rare tropical vine, Ancistrocladus korupensis of Central Africa. This 
class of compounds has been demonstrated to be effective in inhibiting 
the ability of HIV to replicate and infect cells. The compounds also 
have antimalaria activity. Therefore, the dimeric alkaloids appear to 
comprise a novel class of antiviral and antiparasitic drugs that may be 
very useful by themselves or in combination with other treatments.

Dimeric Arylisoquinoline Alkaloids and Synthesis Methods Thereof

G Bringmann, MR Boyd, R Gotz, TR Kelly (NCI)
Serial No. 08/363,684 filed 23 Dec 94 (U.S. Patent 5,578,729 issued 26 
Nov 96) and Serial No. 08/721,084 filed 24 Sep 96 (U.S. Patent 
5,786,482 issued 28 Jul 98)

    The present invention relates to novel compounds and to a new 
method of chemical synthesis of known and new dimeric arylisoquinoline 
alkaloids. These compounds are members of a general class known as 
naphthylisoquinoline alkaloids. These dimeric alkaloids have been found 
to be effective inhibitors of HIV replication in human immune cells. 
The compounds also have antimalarial activity. The method of this 
invention provides access not only to known but also heretofore unknown 
medically useful compounds. The invention also provides for new dimeric 
arylisoquinoline compounds and derivative thereof.

Monomeric Naphthylisoquinoline Alkaloids and Synthesis Methods 
Thereof

G Bringmann, R Gotz, MR Boyd (NCI)
Serial No. 08/279,291 filed 22 Jul 94 (U.S. Patent 5,552,550 issued 03 
Sep 96) and Serial No. 08/674,362 filed 01 Jul 96 (U.S. Patent 
5,763,613 issued 09 Jun 98)

    Monomeric naphthylisoquinoline alkaloids and their derivatives are 
medically useful for the treatment of parasitic infections including 
malaria. However, these particular alkaloids are available in a limited 
supply since they are obtained from scarce plants which have a limited 
geographic distribution. This invention embodies methods for the 
preparation of monomeric naphthylisoquinoline alkaloids, including the 
antiparasitic korupensamines and related compounds, as well as non-
korupensamines. New, medically useful, naphthylisoquinoline compounds 
and derivatives are also described.

Monomeric and Dimeric Arylisoquinoline Alkaloids and Derivatives 
Thereof

G Bringmann, MR Boyd, M Wenzel (NCI)
Serial No. 09/001,801 filed 31 Dec 97

    The present invention provides new monomeric derivatives of the C-
8'-7 linked naphthylisoquinoline alkaloid dioncophylline D. The 
invention also provides new C-4 substituted monmeric arylisoquinoline 
alkaloid derivatives. The present invention furthermore provides novel 
dimeric arylisoquinoline alkaloids comprised of coupled first and 
second arylisoquinoline monomers, wherein either or both of said 
monomer(s) is (are) monomeric compound(s) of the present invention.
    Monomeric and dimeric compounds of the present invention have 
medically useful properties, such as antimicrobial properties, more 
specifically antimalarial and antiviral properties. Monomeric compounds 
of the present invention are also useful as building blocks or 
intermediates for synthesis of novel dimeric arylisoquinoline 
alkaloids.

Michellamine Antiviral Agents, Compositions, and Treatment Methods

MR Boyd, JH Cardellina, KP Manfredi, JW Blunt, LK Pannell, JB McMahon, 
RJ Gulakowski, GM Cragg, G Bringmann, D Thomas, J Jato (NCI)
Serial No. 08/049,824 filed 19 Apr 93 (U.S. Patent 5,455,251 issued 03 
Oct 95) and Serial No. 08/457,677 filed 01 Jun 95 (U.S. Patent 
5,654,432 issued 05 Aug 97)

    Michellamines, structurally novel naphthalene 
tetrahydroisoquinoline alkaloids, are a new class of antiviral 
compounds present in the plant Ancisrocladus korupensis. The 
Ancitrocladaceae is a small paleotropical family, with 20 species known 
from Asia and tropical Africa. A. korupensis contains three distinct 
michellamines, A, B, and C. Michellamine B, the most prevalent and 
potent of the three, is capable of inhibiting two distinct stages of 
the HIV life cycle. the compound is able to inhibit HIV-induced cell 
killing of infected cells but has to effect on HIV virons or initial 
binding of HIV to target cells. In addition, michellamine B inhibits 
the enzymatic activity of both the normal HIV reverse transcriptase and 
the activity of several mutant transcriptases which are resistant to 
several nonnucleoside inhibitors. The claims of this invention relate 
to michellamine compounds and derivatives, methods for the isolation of 
the michellamines from A. korupensis, and methods for the 
administration of these antiviral compounds for treating patients 
infected with HIV. Licenses of this invention will be required to 
comport with all applicable federal and country-of-collection policies 
relating to biodiversity.

Antimalarial Korupensamines and Pharmaceutical Composition and 
Medical Uses Thereof

MR Boyd, G Francois, G Bringmann, YF Hallock, KP Manfredi, JH 
Cardellina (NCI)
Serial No. 08/195,260 filed 14 Feb 94 (U.S. Patent 5,409,938 issued 25 
Apr 95)

    The class of compounds known as korupensamines exhibit in vitro and 
in viro antimalarial activity and offer a potent new means for treating 
and controlling this devastating disease. As many as 2-3 million people 
worldwide die from malaria each year, and many more suffer from long-
term chronic infection. The deadliest malarial parasites have become 
resistant to previously effective antimalarial drugs such as 
chloroquine and other clinically useful agents; therefore, effective 
new antimalarial drugs are urgently needed. These korupensamine 
compounds, which are isolated from a new species of the plant genus 
Ancistrocladus which is found in tropical Africa and southern and 
southeast Asia, effectively inhibit the growth, reproduction, and 
pathologic effects of a broad spectrum of Plasmodia parasites when 
given alone or in conjunction with previously available antimalarial 
agents. Licensees of this invention will be required to comport with 
all applicable federally and country-of-collection policies relating to 
biodiversity.

Antimalarial Napthylisoquinoline Alkaloids and Pharmaceutical 
Compositions and Medicinal Uses Thereof

G Francois, G Bringmann, JD Phillipson, MR Boyd, LA Assi, G Dochez, C 
Schneider, G Timperman (NCI)
Serial No. 08/195,547 filed 14 Feb 94 (U.S. Patent 5,639,761 issued 17 
Jun 97) and Serial No. 08/843,582 filed 16 Apr 97

    This is a new class of napthylisoquinoline alkaloid compounds, 
present in plant species of the Ancistrocladaceae and Dionocophyllaceae 
plant families which

[[Page 55882]]

are found in tropical Africa and southern and southeast Asia, that 
exhibit effective antimalarial properties and offer important new 
weapons in the treatment of this devastating disease. The deadliest 
malarial parasites have become resistant to previously effective 
antimalarial drugs; therefore, effective new antimalarial drugs are 
urgently needed. These new naphthylisoquinoline compounds effectively 
inhibit the growth, reproduction, and pathologic effects of a broad 
spectrum of Plasmodia parasites, including drug-resistant strains.

    Dated: October 13, 1998.
Jack Speigel,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer.
[FR Doc. 98-27960 Filed 10-16-98; 8:45 am]
BILLING CODE 4140-01-M