Note : Les revendications sont présentées dans la langue officielle dans laquelle elles ont été soumises.
30
CLAIMS
1. Neuroserpins of the formulas I and II
I: Neuroserpin of the human
II: Neuroserpin of the mouse
Including the separate, coding and coded sequences of these compounds of
the formulas I or II, including the separate partial sequences of the coding
and coded
sequences of these compounds of the formulas I or II, including the coding or
coded
sequences or partial sequences of the corresponding splice variants of the
compounds of the formulas I or II, including the coding or coded sequences or
partial
sequences of the corresponding alleles of the compounds of the formulas I or
II,
including all sequence variants of the coding or coded sequences, or parts
thereof,
of the compounds of formulas I or II, whose biological activity is equal or
similar to
that of the compounds of the formulas I or II, for example sequence variants
of the
compounds of the formulas I or II, which differ in the not conserved amino
acid
sequence positions of the sequence of the formulas I or II, including the
sequences
hybridizing to the coding sequences, or parts thereof, under stringent
conditions,
including the translation products of the sequences hybridizing to the coding
sequences of the compounds of the formulas I or II, or to parts thereof, under
stringent conditions, including the nucleotide sequences coding the proteins
coded
by the compounds of formulas I or II, or parts thereof, but, as a result of
the use of
different alternative codons, are degenerated with regard to the nucleotide
sequences defined by the compounds of the formulas I or II.
2. Medicament, characterized in that it contains as at least one active
compound either the coded sequence or the coding sequence of the compound of
the formula I or of the formula II, or the separate partial sequences of the
coded and
coding sequences of these compounds of the formulas I or II, including the
coding or
coded sequences or partial sequences of the corresponding splice variants of
the
compounds of the formulas I or II, including the coding or coded sequences or
partial
sequences of the corresponding alleles of the compounds of the formulas I or
II,
including all sequence variants of the coding or coded sequences, or parts
thereof,
of the compounds of formulas I or II, whose biological activity is equal or
similar to
31
that of the compounds of the formulas I or II, for example sequence variants
of the
compounds of the formulas I or II, which differ in the not conserved amino
acid
sequence positions of the sequence of the formulas I or II, including the
sequences
hybridizing to the coding sequences, or parts thereof, under stringent
conditions,
including the translation products of the sequences hybridizing to the coding
sequences of the compounds of the formulas I or II, or to parts thereof, under
stringent conditions, including the nucleotide sequences coding the proteins
coded
by the compounds of formulas I or II, or parts thereof, but, as a result of
the use of
different alternative codons, are degenerated with regard to the nucleotide
sequences defined by the compounds of the formulas I or II.
3. Medicament, characterized in that it contains as at least one active
compound a substance which changes the function of the coded sequence of the
compounds of formulas I or II, for example, in that it reduces or increases
the
protease inhibitory activity of the coded protein, or a part thereof, or in
that it
shortens or prolongs the time of presence of the coded protein at its place of
action
in the body.
4. Medicament, characterized in that it contains as at least one active
compound a substance which changes the expression of the coding or coded
sequences of the compounds of formulas I or II, for example in that it
enhances or
inhibits the transcription of the mRNA or in that it enhances or inhibits the
translation
of the coded sequences of the compounds of formulas I or II.
5. Medicament according to claim 2, 3, or 4, characterized in that it
prevents or reduces the growth, the expansion, the infiltration and the
metastasis of
primary and metastatic tumors, as for example brain tumors or tumors of the
retina.
6. Medicament according to claim 2, 3, or 4, characterized in that it
contributes to the minimization of the tissue destruction in stroke, including
brain
infarction and ischemia, intracerebral hemorrhage, and subarrachnoid
hemorrhage,
as for example by exerting a protecting effect on the cells of the so-called
penumbra
zone surrounding the necrotic tissue.
32
7. Medicament according to claim 2, 3, or 4, characterized in that it
contributes to the minimization of the tissue destruction in traumatic brain
injury, as
for example by exerting a protective effect on the cells of the so-called zone
surrounding the necrotic tissue.
8. Medicament according to claim 2, 3, or 4, characterized in that it
prevents,
ameliorates or cures the negative effects caused by neurodegenerative
diseases.
9. Medicament according to claim 2, 3, or 4, characterized in that it
prevents, ameliorates or cures the negative effects caused by
neuroinflammatory
diseases, as for example multiple sclerosis.
10. Medicament according to claim 2, 3, or 4, characterized in that it reduces
or prevents negative effects on brain tissue caused by epileptic seizures.
11. Medicament according to claim 2, 3, or 4, characterized in that it
contributes to the rescue of endangered neurons, as for example neurons
endangered by hypoxia and ischemia, excitotoxicity, neuroinflammatory diseases
and processes, epileptic seizures, and cancerous neoformations.
12. Medicament according to claim 2, 3, or 4, characterized in that it
contributes to axonal regeneration and/or restoration of synaptic integrity
and
functions.
13. Medicament according to claim 2, 3, or 4, characterized in that it
prevents, ameliorates, or cures retinal disorders, as for example retinal
degeneration
and retinal neoangiogenesis.
14. Medicament according to claim 2, 3, or 4, characterized in that it
prevents the apoptosis of cells of the nervous system.
15. Medicament according to claim 14, characterized in that the apoptosis is
an apoptosis in connection with damages of the nervous tissue, for example
infarct
of the brain and ischemic stroke, or hemorrhage of the brain, or trauma of the
brain.
33
16. Medicament according to claim 14, characterized in that the apoptosis is
an apoptosis in connection with damages of the nervous tissue, which occur due
to
lack of oxygen or glucose or due to intoxication.
17. Medicament according to claim 14, characterized in that the apoptosis is
an apoptosis in connection with epileptic seizures.
18. Medicament according to claim 14, characterized in that the apoptosis is
an apoptosis in connection with neurodegenerative diseases and inherited
genetic
deficiencies of the nervous system.
19. Medicament according to claim 2, 3, or 4, characterized in that it
influences the regeneration of injured, damaged, underdeveloped, or
maldeveloped
brain tissue and/or nervous tissue.
20. Medicament according to claim 2, 3, or 4, characterized in that it
enhances the reorganization of the brain or nervous areas that have remained
intact
after brain and/or nerve injuries or after the destruction or damage of brain
areas.
21. Medicament according to claim 2, 3, or 4, characterized in that it
prevents, ameliorates, or cures pathological pain syndromes.
22. Medicament according to claim 2, 3, or 4, characterized in that it
contributes to the improvement of the brain performance in healthy persons, as
well
as in persons with reduced brain performance.
23. Medicament according to claim 2, 3, or 4, characterized in that it
ameliorates the learning and memory functions in healthy persons, as well as
in
persons with reduced learning and memory functions.
24. Medicament according to claim 2, 3, or 4, characterized in that it
ameliorates or cures disorders in the field of disorders of the psychic
wellness, or the
psychosomatic state of health, as for example nervosity or ~inner unrest".
34
25. Medicament according to claim 2, 3, or 4, characterized in that it
prevents, ameliorates or cures disorders in the field of the emotional
functions, as for
example states of anxiety.
26. Medicament according to claim 2, 3, or 4, characterized in that it
prevents, ameliorates or cures psychiatric disorders.
27. Medicament according to claim 26, characterized in that the psychiatric
disorder is a disorder in the field of schizophrenia and schizophrenia-like
disorders,
including chronic schizophrenia, chronic schizo-affective disorders,
unspecific
disorders, including acute and chronic schizophrenia of various
symptomatologies,
as for example severe, non-remitting ~Kraepelinic" schizophrenia, or as for
example
the DSM-III-R-prototype of the schizophrenia-like disorders, including
episodic
schizophrenic disorders, including delusionic schizophrenia-like disorders,
including
schizophrenia-like personality disorders, as for example schizophrenia-like
personality disorders with mild symptomatics, including schizotypic
personality
disorders, including the latent forms of schizophrenic or schizophrenia-like
disorders,
including non-organic psychotic disorders.
28. Medicament according to claim 26, characterized in that the psychiatric
disorder is a disorder in the field of the endogenic depressions or in the
field of manic
or manic-depressive disorders.
29. Medicament according to claim 2, 3, or 4, characterized in that it
prevents, ameliorates or cures disorders of the brain due to at least one
protease.
30. Medicament according to claim 29, characterized in that the protease is
tissue-type plasminogen activator, abbreviated as tPA, urokinase-type
plasminogen
activator, abbreviated as uPA, or plasmin.
31. Medicament according to claim 29, characterized in that it reduces,
prevents, or cures side effects of therapeutically administered tissue-type
plasminogen activator, or urokinase-type plasminogen activator, or another
type of
plasminogen activator, or plasmin.
35
32. Use for the production of recombinant proteins of the coding nucleotide
sequences of the compounds of the formulas I or II, including the separate
partial
sequences of the coding sequences of the compounds of the formulas I or II,
including the coding nucleotide sequences or partial sequences of the
corresponding
splice variants of the compounds of the formulas I or II, including the coding
sequences or partial sequences thereof of the corresponding alleles of the
compounds of the formulas I or II, including all sequence variants of the
coding
sequences, or parts thereof, of the compounds of formulas I or II, whose
translation
products have a biological activity equal or similar to that of the
translation products
of the compounds of the formulas I or II, for example sequence variants of the
compounds of the formulas I or II, which differ in the not conserved amino
acid
sequence positions of the sequence of the formulas I or II, including the
sequences
hybridizing to the coding sequences of the compounds of the formulas I or II,
or parts
thereof, under stringent conditions, including the nucleotide sequences coding
the
proteins coded by the compounds of the formulas I or II, or parts thereof,
but, as a
result of the use of different alternative codons, are degenerated with regard
to the
nucleotide sequences defined by the compounds of the formulas I or II.
33. Use as targets for the development of pharmaceutical drugs, for example
for the inhibition or the enhancement of the protease inhibitory activity of
the coded
proteins of the formulas I or II, of proteins with the coded amino acid
sequences of
the compounds of the formulas I or II, including the proteins with the
separate partial
sequences of the coded amino acid sequences of the compounds of the formulas I
or II, including the proteins with the coded sequences or partial sequences of
the
corresponding splice variants of the compounds of the formulas I or II,
including the
proteins with the coded amino acid sequences or partial sequences thereof of
the
corresponding alleles of the compounds of the formulas I or II, including all
sequence
variants of the coded sequences, or parts thereof, of the compounds of
formulas I or
II, whose biological activity is equal or similar to the coded sequences of
the
compounds of the formulas I or II, for example sequence variants of the
compounds
of the formulas I or II, which differ in the not conserved amino acid sequence
positions of the sequences of the formulas I or II, including the proteins
with the
coded amino acid sequences, or partial sequences thereof, of the nucleotide
sequences hybridizing to the coding sequences of the compounds of the formulas
I
or II, or parts thereof, under stringent conditions.
36
34. Use as targets for the development of pharmaceutical drugs, for example
for the enhancement or the inhibition of the protease inhibitory activity of
the coded
proteins of the formulas I or II, of the species-homologous proteins, or parts
thereof,
of the compounds of the formulas I or II, as for example the species-
homologous
proteins of the rat, the rabbit, the cow, the sheep, the pig, the primates,
the birds, the
zebra fish, the fruit fly (Drosophila melanogaster), etc., including the
partial
sequences thereof, including the splice variants of the species-homologous
proteins,
including the alleles of the species-homologous proteins, including the
translation
products of the sequences hybridizing under stringent conditions to the
corresponding species-homologous compounds of the formulas I or II, or their
splice
variants, or their alleles, of the coding sequences or partial sequences of
the
compounds of formulas I or II.
35. Use for the spatial structure determination, for example the spatial
structure determination by means of crystallography or nuclear resonance
spectroscopy, of the proteins with the coded amino acid sequences of the
compounds of the formulas I or II, including the proteins with the separate
partial
sequences of the coded amino acid sequences of the compounds of the formulas I
or II, including the proteins with the coded sequences or partial sequences of
the
corresponding splice variants of the compounds of the formulas I or II,
including the
proteins with the coded amino acid sequences, or partial sequences thereof, of
the
corresponding alleles of the compounds of the formulas I or II, including all
sequence
variants of the coded sequences, or parts thereof, of the compounds of the
formulas
I or II, whose biological activity is equal or similar to that of the coded
sequences of
the compounds of the formulas I or II, for example sequence variants of the
compounds of the formulas I or II, which differ in the not conserved amino
acid
sequence positions of the sequences of the formulas I or II, including the
translation
products with the sequences hybridizing to the coding sequences of the
compounds
of the formulas I or II, or parts thereof, under stringent conditions,
including the
species-homologous proteins of the compounds of the formulas I or II, for
example
the species-homologous proteins of the rat, the rabbit, the cow, the sheep,
the pig,
the primates, the birds, the zebra fish, the fruit fly (Drosophila
melanogaster), etc.,
including the partial sequences thereof, as for example the separate catalytic
domains.
37
36. Use for the prediction of the protein structure by means of computerized
protein structure prediction methods, of the coded amino acid sequences of the
compounds of the formulas I or II, including the separate partial sequences of
the
coded amino acid sequences of the compounds of the formulas I or II, including
the
coded sequences or partial sequences of the corresponding splice variants of
the
compounds of the formulas I or II, including the coded amino acid sequences,
or
parts thereof, of the corresponding alleles of the compounds of the formulas I
or II,
including all sequence variants of the coded sequences, or parts thereof, of
the
compounds of the formulas I or II, whose biological activity is equal or
similar to that
of the coded sequences of the compounds of the formulas I or II, for example
sequence variants of the compounds of the formulas I or II, which differ in
the not
conserved amino acid sequence positions of the sequences of the formulas I or
II,
including the amino acid sequences of the translation products of the
sequences
hybridizing to the coding sequences of the compounds of the formulas I or II,
or parts
thereof, under stringent conditions, including sequences of the species-
homologous
compounds of the compounds of the formulas I or II, for example the sequences
of
the species-homologous compounds of the rat, the rabbit, the cow, the sheep,
the
pig, the primates, the birds, the zebra fish, the fruit fly (Drosophila
melanogaster),
etc., including the partial sequences of the species-homologous compounds, as
for
example the sequences of the catalytic domains of the species-homologous
compounds.
37. Use as targets for the development of pharmaceutical drugs , for
example for the inhibition or the enhancement of the protease inhibitory
activity of
the coded proteins of the formulas I or II, of the spatial structure of the
coded amino
acid sequences of the compounds of the formulas I or II, including the spatial
structures of the separate partial sequences of the compounds of the formulas
I or II,
including the spatial structure of the coded sequences or partial sequences of
the
corresponding splice variants of the compounds of the formulas I or II,
including the
spatial structure of the coded sequences or partial sequences of the
corresponding
alleles of the compounds of the formulas I or II, including the spatial
structure of all
sequence variants of the coded sequences, or parts thereof, of the compounds
of
formulas I or II, whose biological activity is equal or similar to the coded
sequences of
the compounds of the formulas I or II, for example sequence variants of the
38
compounds of the formulas I or II, which differ in the not conserved amino
acid
sequence positions of the sequences of the formulas I or II, including the
spatial
structures of the translation products of the sequences hybridizing to the
coding
sequences of the compounds of the formulas I or II, or parts thereof, under
stringent
conditions, including the spatial structures of the species-homologous
compounds of
the compounds of the formulas I or II, as for example the spatial structures
of the
species homologous compounds, or parts thereof, of the rat, the rabbit, the
cow, the
sheep, the pig, the primates, the birds, the zebra fish, the fruit fly
(Drosophila
melanogaster), etc..
38. Use in gene therapeutical applications in humans and in animals, as for
example as parts of gene therapy vectors or as for example as parts of
artificial
chromosomes, of the coding nucleotide sequences of the compounds of the
formulas I or II, including the separate partial sequences of the coding
sequences of
these compounds of the formulas I or II, including the coding sequences or
partial
sequences of the corresponding splice variants of the compounds of the
formulas I
or II, including the coding sequences or partial sequences of the
corresponding
alleles of the compounds of the formulas I or II, including all sequence
variants of the
coding sequences, or parts thereof, of the compounds of the formulas I or II,
whose
translation products exhibit a biological activity which is equal or similar
to the that of
the translation products of the compounds of the formulas I or II, for example
sequence variants of the compounds of the formulas I or II, which differ in
the not
conserved amino acid sequence positions of the sequences of the compounds of
the
formulas I or II, including the sequences hybridizing to the coding sequences,
or
parts thereof, under stringent conditions, including the nucleotide sequences
coding
the proteins coded by the compounds of the formulas I or II, or parts thereof,
but as a
result of the use of different alternative codons, are degenerated with regard
to the
nucleotide sequences defined by the compounds of the formulas I or II.
39. Use for so-called cell engineering applications for the production of gene
technologically mutated cells, which produce the coded sequences, or parts
thereof,
of the compounds of the formulas I or II, for example for cell-therapeutical
applications as a medicament according to claim 2, 3, 4, 5, 6, 7, 8, 9, 10,
11, 12, 13,
14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 or 31 of
the coding
nucleotide sequences of the compounds of the formulas I or II, including the
39
separate partial sequences of the coding sequences of these compounds of the
formulas I or II, including the coding sequences or partial sequences of the
corresponding splice variants of the compounds of the formulas I or II,
including the
coding sequences or partial sequences of the corresponding alleles of the
compounds of the formulas I or 11, including all sequence variants of the
coding
sequences, or parts thereof, of the compounds of the formulas I or II, whose
translation products exhibit a biological activity which is equal or similar
to that of the
translation products of the compounds of the formulas I or II, for example
sequence
variants of the compounds of the formulas I or II, which differ in the not
conserved
amino acid sequence positions of the sequence of the compounds of the formulas
I
or II, including the sequences hybridizing to the coding sequences, or parts
thereof,
under stringent conditions, including the nucleotide sequences coding the
proteins
coded by the compounds of formulas I or II, or parts thereof, but as a result
of the
use of different alternative codons, are degenerated with regard to the
nucleotide
sequences defined by the compounds of the formulas I or II.
40. Use as antigens for the production of antibodies, as for example
antibodies that inhibit or promote the protease inhibitory function or
antibodies that
can be used for immunohistochemical studies, of the coded amino acid sequences
of
the compounds of the formulas I or II, including the separate partial
sequences of the
coded amino acid sequences of the compounds of the formulas I or II, including
the
coded sequences or partial sequences of the corresponding splice variants of
the
compounds of the formulas I or II, including the coded sequences or partial
sequences of the corresponding alleles of the compounds of the formulas I or
II,
including all sequence variants of the coded sequences, or parts thereof, of
the
compounds of the formulas I or II, whose biological activity is equal or
similar to that
of the coded sequences of the compounds of the formulas I or II, for example
sequence variants of the compounds of the formulas I or II, which differ in
the not
conserved amino acid sequence positions of the sequence of the compounds of
the
formulas I or II, including the translation products or parts thereof, of the
sequences
hybridizing to the coding sequences of the compounds of the formulas I or II,
or parts
thereof, under stringent conditions, including the coded sequences of the
species-homologous compounds of the compounds of the formulas I or II, as for
example the
coded sequences of the species-homologous compounds of the rat, the rabbit,
the
cow, the sheep, the pig, the primates, the birds, the zebra fish, the fruit
fly
40
(Drosophila melanogaster), etc., including the separate partial sequences of
the
coded sequences of the species-homologous compounds of the compounds of the
formulas I or II, as for example the coded amino acid sequence of the
catalytic
domain, or one or more of the other domains or segments.
41. Use for the production of transgenic animals, as for example transgenic
mice, of the coding nucleotide sequences of the compounds of the formulas I or
II,
including the separate partial sequences of the coding sequences of these
compounds of the formulas I or II, including the coding sequences or partial
sequences of the corresponding splice variants of the compounds of the
formulas I
or II, including the coding sequences, or partial sequences, of the
corresponding
alleles of the compounds of the formulas I or II, including all sequence
variants of the
coding sequences, or parts thereof, of the compounds of the formulas I or II,
whose
translation products exhibit a biological activity which is equal or similar
to that of the
translation products of the compounds of the formulas I or II, for example
sequence
variants of the compounds of the formulas I or II, which differ in the not
conserved
amino acid sequence positions of the sequences of the compounds of the
formulas I
or II, including the sequences hybridizing to the coding sequences, or parts
thereof,
under stringent conditions, including the nucleotide sequences coding the
proteins
coded by the compounds of the formulas I or II, or parts thereof, but as a
result of the
use of different alternative codons, are degenerated with regard to the
nucleotide
sequences defined by the compounds of the formulas I or II.
42. Use for the inactivation or the mutation of the corresponding gene by
means of gene targeting techniques, as for example the elimination of the gene
in
the mouse through homologous recombination or the replacement of the gene by a
mutated form thereof, of the coding nucleotide sequences of the compounds of
the
formulas I or II, including the separate partial sequences of the coding
sequences of
these compounds of the formulas I or II, including the coding sequences, or
partial
sequences, of the corresponding splice variants of the compounds of the
formulas I
or II, including the coding sequences, or partial sequences, of the
corresponding
alleles of the compounds of the formulas I or II, including all sequence
variants of the
coding sequences, or parts thereof, of the compounds of the formulas I or II,
whose
translation products exhibit a biological activity which is equal or similar
to that of the
translation products of the compounds of the formulas I or II, for example
sequence
41
variants of the compounds of the formulas I or II, which differ in the not
conserved
amino acid sequence positions of the sequence of the compounds of the formulas
I
or II, including the sequences hybridizing to the coding sequences, or parts
thereof,
under stringent conditions, including the nucleotide sequences coding the
proteins
coded by the compounds of the formulas 1 or II, or parts thereof, but as a
result of the
use of different alternative codons, are degenerated with regard to the
nucleotide
sequences defined by the compounds of the formulas I or II.
43. Use for the diagnostics of disorders in the gene corresponding to the
compound of the formula I, of the coding nucleotide sequences of the compounds
of
the formulas I or II, including the separate partial sequences of the coding
sequences of these compounds of the formulas I or II, including the coding
sequences or partial sequences of the corresponding splice variants of the
compounds of the formulas I or II, including the coding sequences, or partial
sequences, of the corresponding alleles of the compounds of the formulas I or
II,
including all sequence variants of the coding sequences, or parts thereof, of
the
compounds of the formulas I or II, whose translation products exhibit a
biological
activity which is equal or similar to that of the translation products of the
compounds
of the formulas I or II, for example sequence variants of the compounds of the
formulas I or II, which differ in the not conserved amino acid sequence
positions of
the sequences of the compounds of the formulas I or II, including the
sequences
hybridizing to the coding sequences, or parts thereof, under stringent
conditions,
including the nucleotide sequences coding the proteins coded by the compounds
of
the formulas I or II, or parts thereof, but as a result of the use of
different alternative
codons, are degenerated with regard to the nucleotide sequences defined by the
compounds of the formulas I or II.
44. Use as a starting sequence for gene technological modifications aimed
at the production of medicaments or gene therapy vectors which exhibit changed
properties as compared with the corresponding medicaments or gene therapy
vectors containing the coding nucleotide sequence of the compounds of formulas
I or
II, for example changed protease inhibitory activity, changed protease
inhibitory
specificity, or changed pharmacokinetic characteristics, of the coding
nucleotide
sequences of the compounds of the formulas I or II, including the separate
partial
sequences of the coding sequences of these compounds of the formulas I or II,
42
including the coding sequences or partial sequences of the corresponding
splice
variants of the compounds of the formulas I or II, including the coding
sequences, or
partial sequences, of the corresponding alleles of the compounds of the
formulas I or
II, including all sequence variants of the coding sequences, or parts thereof,
of the
compounds of the formulas I or II, whose translation products exhibit a
biological
activity which is equal or similar to that of the translation products of the
compounds
of the formulas I or II, for example sequence variants of the compounds of the
formulas I or II, which differ in the not conserved amino acid sequence
positions of
the sequences of the compounds of the formulas I or II, including the
sequences
hybridizing to the coding sequences, or parts thereof, under stringent
conditions,
including the nucleotide sequences coding the proteins coded by the compounds
of
the formulas I or II, or parts thereof, but as a result of the use of
different alternative
codons, are degenerated with regard to the nucleotide sequences defined by the
compounds of the formulas I or II.