Therapeutic molecules derived from snake venom

Details Therapeutic molecules derived from snake venom Therapeutic molecules derived from snake venom

2000-07-26

2003-09-02

Low, Christopher S. F. (Department: 1653)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Peptide containing doai

C514S017400, C530S327000, C530S328000, C530S330000, C530S334000, C530S344000, C536S023500, C435S069100, C435S252300, C435S320100

Reexamination Certificate

active

06613745

ABSTRACT:

FIELD OF THE INVENTION
The present invention relates generally to peptide molecules and to derivatives, homologues, analogues and mimetics thereof capable of inducing or facilitating analgesia or partial analgesia alone or in combination with other analgesic molecules. The present invention also contemplates a method of inducing or facilitating analgesia or partial analgesia by the administration of a peptide or a derivative, homologue, analogue or mimetic thereof. The amino acid sequence of the peptide molecules of the present invention are derived from or based on amino acid sequences of snake venom toxins, and, in particular, &agr;-neurotoxins.
BACKGROUND OF THE INVENTION
The increasing demand for improved and more efficacious analgesics is providing the incentive for the pharmaceutical industry to consider new approaches for identifying and designing new therapeutic molecules. One source considered to be of potential interest in the quest for new pharmaceutical agents is the identification of molecules from the natural environment including molecules from life forms in the environment. Much effort is now being spent, therefore, on screening aquatic environments, river beds, coral, plants, microorganisms and higher animals for potentially useful molecules. This search is often referred to as “natural product screening”. The level of biodiversity in the Asian and Australasian regions provides a particularly useful target for natural product screening.
Reptiles are one of the oldest life forms on earth of which snakes form a particularly interesting group. Many venomous snakes have evolved toxin molecules such as &agr;-neurotoxins which are highly effective in inducing a range of neurological dysfunctions.
Whereas snake venom has been studied to the extent of producing antidotes and antivenene, snakes have not been extensively studied as a potential source of therapeutic molecules.
In work leading up to the present invention, the inventors studied snake venom from a particularly venomous snake, the King cobra (
Ophiophagus hannah
). This snake is broadly distributed in India, Burma, Thailand, Malaysia, Indochina, Southern China, Indonesia, Japan and the Philippines (Tin et al, 1991). To date, six &agr;-neurotoxins have been isolated from the king cobra venom (Joubert, 1973; Chang et al, 1993; Song et al, 1994). Little, however, is known of the pharmacological properties of those toxins.
The inventors have now surprisingly determined that peptide molecules having an amino acid sequence or derived from or based on portions of snake venom toxins have analgesic properties.
SUMMARY OF THE INVENTION
One aspect of the present invention provides a peptide comprising a sequence of amino acids having at least 60% similarity to a sequence of amino acids from a portion of a toxin from snake venom and which peptide is capable of inducing or facilitating analgesia or a derivative, homologue, analogue or mimetic of said peptide.
Another aspect of the present invention relates to a peptide comprising a sequence of amino acids having at least 60% similarity to an amino acid sequence from a portion of an &agr;-neurotoxin from venom from a snake of the family of snakes selected from Elapidae, Viperidae, Colubridae or Crotalidae and which peptide is capable of inducing or facilitating analgesia or a derivative, homologue, analogue or mimetic of said peptide.
Yet another aspect of the present invention is directed to a peptide comprising the amino acid sequence N P F P T (SEQ ID NO:1) and which peptide is capable of inducing or facilitating analgesia or a derivative, homologue, analogue or mimetic of said peptide.
Still yet another aspect of the present invention provides a peptide having the amino acid sequence N P F P T X
1
X
2
K R X
3
X
4
(SEQ ID NO:2) wherein X
1
, X
2
, X
3
, X
4
may be the same or different and each is any amino acid residue wherein said peptide is capable of inducing of facilitating analgesia or a derivative, homologue, analogue or mimetic of said peptide.
In yet another aspect of the present invention, there is provided a peptide having an amino acid sequence selected from the list consisting of:
N P F P T W R K R P G (SEQ ID NO:3);
N P F PT R K R P (SEQ ID NO:4);
N P F P T W R K R P (SEQ ID NO:5); and
N P F P T W K R K H (SEQ ID NO:6);
or a derivative, homologue, analogue or mimetic of one or more of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5 or SEQ ID NO:6 and wherein said peptide is capable of inducing or facilitating analgesia.
The present invention also provides a composition comprising a peptide as defined above alone or in combination with one or more pharmaceutically acceptable carriers and/or diluents and/or one or more other active molecules such as an analgesic molecule or compound.
Still another aspect of the present invention contemplates a method of inducing or facilitating analgesia said method comprising administering a peptide as hereinbefore defined for a time and under conditions sufficient to induce pain relief.
Even yet another aspect of the present invention is directed to the use of a peptide as hereinbefore defined in the manufacture of a medicament for inducing or facilitating analgesia.
The present invention further extends to antibodies to the peptides as hereinbefore defined.
The peptides of the present invention are referred to as “analgesic” peptides.
Throughout this specification, unless the context requires otherwise, the word “comprise”, or variations such as “comprises” or “comprising”, will be understood to imply the inclusion of a stated element or integer or group of elements or integers but not the exclusion of any other element or integer or group of elements or integers.
Bibliographic details of the publications referred to by author in this specification are collected at the end of the description.
Sequence Identity Numbers (SEQ ID NOs.) for the amino acid sequences referred to in the specification are defined following the bibliography.
Single and three letter abbreviations used throughout the specification are defined in Table 1.
TABLE 1
Single and three letter amino acid abbreviations
Three-letter
One-letter
Amino Acid
Abbreviation
Symbol
Alanine
Ala
A
Arginine
Arg
R
Asparagine
Asn
N
Aspartic acid
Asp
D
Cysteine
Cys
C
Glutamine
Gln
Q
Glutamic acid
Glu
E
Glycine
Gly
G
Histidine
His
H
Isoleucine
Ile
I
Leucine
Leu
L
Lysine
Lys
K
Methionine
Met
M
Phenylalanine
Phe
F
Proline
Pro
P
Serine
Ser
S
Threonine
Thr
T
Tryptophan
Trp
w
Tyrosine
Tyr
Y
Valine
Val
V
Any residue
Xaa
X


REFERENCES:
patent: A2130708 (1971-12-01), None
patent: A1-9208472 (1992-05-01), None
Joubert, Biochem. Biophys. Acta 317, 85-98 (1973).*
Chang et al., Sequence characterization of a novel a-neurotoxin from the king cobra (Ophiophagus hannah) venom. Biochem. Biohys. Res. Comm. 191, 214-223 (Feb. 1993).*
Song, et al., Purification, sequence and pharmaceutical studies of a new alpha-neurotoxin from Ophiophagus hannah venom. Toxicon 32, 537-538 (1994) abstract.*
Pu et al., A novel analgesic toxin (Hannalgesin) from the venom of king cobra (Ophiophagus hannah). Toxicon 33, 1425-1431 (1995).*
Database WPI on Questel, JP 57-116 019 A Jul. 19, 1982, English Abstract only.
Database WPI on Questel, CN 1 088 832 A Jul. 6, 1994, English Abstract only.
Dateabase WPI on Questel, CN 1 102 570 A May 17, 1995, English Abstract only.

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