Drug – bio-affecting and body treating compositions – Extract – body fluid – or cellular material of undetermined...
Reexamination Certificate
2001-05-29
2003-04-08
Jordan, Charles T. (Department: 3644)
Drug, bio-affecting and body treating compositions
Extract, body fluid, or cellular material of undetermined...
C119S208000
Reexamination Certificate
active
06544560
ABSTRACT:
The present invention relates to the culture of sessile marine animals for extraction of marine pharmaceuticals. In particular, the present invention relates to methods and devices for the culture of marine organisms known as tunicates.
BACKGROUND OF THE INVENTION
Over the past years, a systematic screening of many kinds of marine organisms has been undertaken to discover natural compounds that might have pharmacological uses. Sessile marine invertebrates have been shown to be worthwhile sources of potentially useful natural products. Among these invertebrates, tunicates or ascidians (Tunicata, Ascidiacea) have turned out to be especially interesting as sources for such natural products. Research in various places has shown that several compounds isolated from tunicates, principally the ecteinascidins and didemnins, have a potential for therapy of human cancers.
Thus, for example, extraction of the tunicate
Ecteinascidia turbinata
has yielded ecteinascidin 743 and other antitumour ecteinascidin compounds, while extraction of the tunicate
Aplidium albicans
gives dehydrodidemnin B and other antitumour didemnin compounds. Likewise, many active compounds have been isolated from other sessile marine organisms, notably from sponges. Many of these compounds extracted from tunicates, sponges and other such organisms have a complex structure which makes chemical synthesis difficult.
Thus, for ecteinascidin 743 and many other interesting compounds, it remains a matter of collecting the organism in bulk from nature, for subsequent isolation of the desired active compound.
Ecteinascidia turbinata
(Herdman, 1880 l
Ascidiacea, Perophoridae
), is a colonial ascidian of transparent tunic and usually bright orange colour. A colony consists of a dense group or cluster of elongated, somewhat club-shaped zooids, which are connected at their bases by a network of stolons that adheres to the surface of the object on which the colony grows. The colonies normally live in shallow water (0 to 15 m) and in lagoons, growing on red mangrove roots, rocks, shells, turtle grass, bottom sand or on plants such as Caulerpa or Posidonia species. It is common and widely distributed in mangroves areas of the Caribbean Sea and the Mediterranean Sea.
E. turbinata
reproduces by both a sexual cycle, in which eggs are hatched internally within a brood pouch and larvae are released when a zooid reaches maturation or asexually, by budding from the stolon or base.
Ecteinascidia turbinata
is currently collected in the Caribbean from underwater mangrove roots, where it occurs in the colonies. Diving is not without difficulties, and finding the colonies among the tangled roots presents further problems. Moreover, the collecting must be done in a sustainable manner.
Accordingly, development of novel drugs from these sources has been hindered by the fact that these animals are not abundant enough in nature and sustainable collection of sufficient mass to provide the amounts needed for manufacturing of their active components as drugs is difficult.
OBJECT OF THE INVENTION
The present invention is concerned with the provision of methods and devices for culture of tunicates and other sessile marine organisms. In particular, the present invention is directed at the production by farming of
Ecteinascidia turbinata.
SUMMARY OF THE INVENTION
The present invention provides a method of producing a marine pharmaceutical by extraction from a sessile marine organism, which method comprises positioning a plurality of like substrates in sea water, growing the organism on the plurality of substrates, harvesting the grown organism, and extracting the pharmaceutical from the harvested organism.
In a related aspect, the present invention provides a method of farming a sessile marine organism intended for extraction of a marine pharmaceutical, which method comprises positioning a plurality of like substrates in sea water, allowing larvae from a colony of the organism to seed the substrates, growing the organism on the plurality of substrates, and harvesting the grown organism.
In another related aspect, the present invention provides a method of farming a sessile marine organism intended for extraction of a marine pharmaceutical, which method comprises positioning a plurality of like substrates in sea water, transplanting the organism onto the substrates, growing the organism on the plurality of substrates, and harvesting the grown organism.
PREFERRED EMBODIMENTS
We prefer that the marine organism is
Ecteinascidia turbinata
and the marine pharmaceutical is an ecteinascidin compound, particularly ecteinascidin 743. In another preferred embodiment, the marine organism is
Aplidium albicans,
and the marine pharmaceutical is a didemnin compound, particularly dehydrodidemnin B.
This invention provides a device and a method, which allows for monoculture of sessile marine animals, in particular of tunicates such as
E. turbinata,
in clean waters adjacent to or at a distance from their native locations, and their harvesting in amounts sufficient for industrial production of drugs from their extracts. In some versions, the invention is particularly adapted for application in areas of Mediterranean coastal lagoons, harbour areas, or in appropriately constructed tanks or canals, while in other versions it is particularly suited for use in Caribbean waters, notably Caribbean mangrove swamp, keys and canals, harbour areas, or in an appropriately constructed tanks growing on red mangrove roots, rocks, shells, turtle grass, bottom sand or on plants.
In the farming methods of this invention, one aspect involves transplanting the organism onto the substrates which then grow for harvesting. In one embodiment, individual organisms are transplanted onto the substrates. Alternatively, for example with sponges, fragments of organisms are transplanted onto the substrates.
For seeding by implants, small pieces (say about 20 gr.) cut off from young, growing colonies are transported to the device and preferably placed into support baskets or boxes or affixed to the holes of a net or to the spaces between the individual ropes or rods of the device. Fixation can be achieved if needed, by using lengths of string, rubber, or any other method that maintains contact between the stolon of the colony and the device surface. Asexual growth of the organisms gives rise to net increase of mass of tunicates under appropriate water conditions.
Another aspect of the farming method of this invention involves allowing larvae from a colony of the organism to seed the substrates which then grow for harvesting. In one embodiment, the substrates are placed adjacent the colony. Alternatively, at least one collector is placed adjacent the colony to collect larvae, and then larvae on the collector are subsequently employed to seed the substrates. In this alternative, the substrates can be in the general locality of the colony so that local handling of the collector with larvae is all that is needed, or the substrates can be remote from the colony, so that the collectors with larvae are transported to be adjacent the substrates.
For this aspect involving the use of collectors, the present invention further involves a method of harvesting tunicates, wherein a multiplicity of larval collectors are positioned in the vicinity of tunicate colonies, and larvae released from the colonies are allowed to collect on the larval collectors. The loaded collectors can then be left in position for the larvae to mature, or transferred to a fresh area for the larvae to mature.
The present invention also provides larval collectors each comprising a support which can be secured to a mangrove root at a tunicatecolony, with one or more larval substrates for receiving larvae from the colony. The collector of this invention preferably comprises a support with elongate cords or other form of substrate extending therefrom to mimic mangrove roots suitable for colonisation by the larvae. The support is preferably generally circular, with the substrate at the periphery. The support suitably has a central
Bullent Kukurtcu Targotay
Carlos Barbero Garcia
Santiago Naranjo Lozano
Silvia Martin Benitez
Banner & Witcoff , Ltd.
Jordan Charles T.
Linek Ernest V.
Nelson Judith A.
Pharma Mar S.A.
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