US2008312158A1PendingUtilityA1
Semaphorin Gene Family
Est. expirySep 13, 2013(expired)· nominal 20-yr term from priority
A61P 37/00A61P 35/00A61P 31/12C12N 15/8509A01K 2217/05A01K 2217/075A01K 2267/0318C07K 14/4703A01K 2267/01C12N 2710/24122A01K 2267/03A61K 38/00C07K 14/005C07K 14/705A61P 25/00A01K 67/68
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Claims
Abstract
A novel class of proteins, semaphorins, nucleic acids encoding semaphorins, semaphorin peptides, and methods of using semaphorins and semaphorin-encoding nucleic acids are disclosed. Semaphorin peptides and receptor agonists and antagonists provide potent modulators of nerve cell growth and regeneration. The invention provides pharmaceutical compositions, methods for screening chemical libraries for regulators of cell growth/differentiation; semaphorin gene-derived nucleic acids for use in genetic mapping, as probes for related genes, and as diagnostic reagents for genetic neurological disease; specific cellular and animal systems for the development of neurological disease therapy.
Claims
exact text as granted — not AI-modified1 . An isolated peptide of at least 5 amino acids comprising a unique portion of a semaphorin, and said peptide has a semaphorin binding specificity.
2 . An isolated peptide according to claim 1 wherein said semaphorin comprises a human semaphorin.
3 . An isolated peptide according to claim 1 wherein the amino acid sequence of said unique portion comprises a sequence selected from the group consisting of:
(a)
[DE]C[QKRAN]N[YFV]I
C[QKRAN]N[YFV]I[RKQT]
(b)
CGT[NG][ASN][YFHG][KRHNQ]
CGT[NG][ASN]XXP
CGT[NG]XXXPX[CD]
CGTXXXXPX[CD]XX[YI]
(c)
[RIQY][GA][LVK][CS]P[FY][DN]
[CS]P[FY][DN]P[DERK][HLD]
GX[GA]X[CS]PY[DN]P
(d)
L[FY]S[GA]T[VNA]A
L[FY]SXTXA[DE][FY]
[FY]S[GA]T[VNA]A[DE][FY]
(e)
L[ND][AK]PNFV
(f)
FFFRE
FF[FY]RE[TN]
FFRE[TN]A
F[FY]RE[TN]A
YFF[FY]RE
[FY]FF[FY]RE
[FY][FY][FY]RE[TN]A
[IV][FY]F[FY][FY]RE
D[KFY]V[FY][FYIL][FYIL][FY]
[VI][FY][FYIL][FYIL]F[RT]X[TN]
[VI][FY][FYIL][FYIL][FY][RT][EDV][TN]
(g)
E[FY]IN[CS]GK
[FY]INCGK[AVI]
(h)
R[VI][AG][RQ][VI]CK
R[VI]X[RQ][VI]CXXD
GK[VAI]XXXR[VAI]XXXCK
(i)
[RKN]W[TAS][TAS][FYL]L[KR]
[FY]L[KR][AS]RL[NI]C
[NI]CS[IV][PS]G
W[TAS][TAS][FYL]LK[ASVIL]XL
W[TAS][TAS]XLKXXLXC
WX[TS]XLKXXLXC
(j)
[FYI[FY][ND]EIQS
[FY]P[FY][FY][FY][ND]E
(k)
GSA[VIL]CX[FY]
SA[VIL]CX[FY]XM
(l)
NS[NA]WL[PA]V
(m)
[VLI]P[EDYSF]PRPG
[VLI]PXP[RA]PGXC
P[EDYSF]PRPG[TQS]C
(n)
DP[HFY]C[AG]W
P[HFY]C[AG]WD
DPXC[AG]WD
CXXXXDPXCXWD
CXXXDPXCXWD
CXXDPXCXWD
CXXCXXXXDXXCXWD
CXXCXXXDXXCXWD
CXXCXXDXXCXWD
4 . An isolated peptide according to claim 1 wherein the amino acid sequence of said unique portion comprises a sequence selected from the group consisting of:
(a)
[DE]C[QKRAN]N[YFV]I
C[QKRAN]N[YFV]I[RKQT]
(b)
CGT[NG][AS][YFHG][KRHNQ]
CGT[NG][ASN][YFH][KRHNQ]
CGT[NG][AS]XXP
(c)
[RIQV][GA][LVK][CS]P[FY][DN]
[CS]P[FY][DN]P[DERK][HLD]
GX[GA]X[CS]PY[DN]P
(d)
L[FY]S[GA]T[VNA]A
L[FY]SXTXA[DE][FY]
[FY]S[GA]T[VNA]A[DE][FY]
(e)
L[ND][AK]PNFV
(f)
FFFRE
FF[FY]RE[TN]
FFRE[TN]A
F[FY]RE[TN]A
YFF[FY]RE
[FY]FF[FY]RE
[FY][FY][FY]RE[TN]A
[IV][FY]F[FY][FY]RE
D[KFY]V[FY][FYL][FYIL][FY]
D[KFY]V[FY][FYIL][FYI][FY]
[VI][FY][FYL][FYIL]F[RT]X[TN]
[VI][FY][FYIL][FYI]F[RT]X[TN]
[VI][FY][FYIL][FYIL]FRX[TN]
[VI][FY][FYL][FYIL][FY][RT][EDV][TN]
(g)
E[FY]IN[CS]GK
[FY]INCGK[AVI]
(h)
R[VI][AG][RQ][VI]CK
R[VI]X[RQ][VI]CXXD
GK[VAI]XXXR[VAI]XXXCK
(i)
[RKN]W[TA][TAS][FYL]L[KR]
[FY]L[KR][AS]RL[NI]C
[NI]CS[IV][PS]G
W[TA][TAS][FYL]LK[ASVIL]XL
W[TAS][TAS][FYL]LK[ASIL]XL
W[TA][TAS]XLKXXLXC
(j)
[FY][FY][ND]EIQS
[FY]P[FY][FY][FY][ND]E
(k)
GSA[VIL]CX[FY]
SA[VI]CX[FY]XM
(l)
NS[NA]WL[PA]V
(m)
[VLI]P[EDYSF]PRPG
[VLI]PXPRPGXC
P[EDYSF]PRPG[TQS]C
(n)
DP[HFY]C[AG]W
P[HFY]C[AG]WD
DPXC[AG]WD
CXXXXDPXCXWD
CXXXDPXCXWD
CXXDPXCXWD
CXXCXXXXDXXCXWD
CXXCXXXDXXCXWD
CXXCXXDXXCXWD
5 . An isolated peptide according to claim 1 wherein the amino acid sequence of said unique portion comprises a sequence selected from the group consisting of:
(a)
DCQNYI
(b)
CGT[NG][AS]XXP
(c)
GX[SC]PYDP
(d)
LYSGT[VNA]A
(e)
LNAPNFV
(f)
[FY]FF[FY]RE
(g)
E[FY]IN[CS]GK
(h)
R[VI]ARVCK
(i)
W[TA][TS][FY]LK[AS]RL
(j)
PFYF[ND]EIQS
(k)
GSAVCX[FY]
(l)
NSNWL[PA]V
(m)
P[ED]PRPG[TQS]C
(n)
DPYC[AG]WD
6 . An isolated antibody that specifically binds a peptide according to claim 1 .
7 . An isolated nucleic acid comprising a nucleotide sequence encoding a peptide according to claim 1 wherein said sequence is joined to a nucleotide not naturally joined to said sequence and said sequence is other than that of the A39 ORF of vaccinia virus.
8 . A cell comprising a nucleic acid according to claim 7 .
9 . A transgenic rodent comprising a nucleic acid according to claim 7 wherein said nucleic acid is xenogeneic to said rodent.
10 . A process for the production of a recombinant unique portion of a semaphorin comprising culturing the cell of claim 8 under conditions suitable for the expression of said peptide, and recovering said peptide.
11 . A method of identifying a pharmacological agent useful in the diagnosis or treatment of disease associated with the binding of a semaphorin to a semaphorin receptor, said method comprising the steps of:
contacting a panel of prospective agents with a peptide according to claim 1 ; measuring the binding of a plurality of said prospective agents to said peptide: identifying from said plurality a pharmacological agent which specifically binds said peptide; wherein said pharmacological agent is useful in the diagnosis or treatment of disease associated with the binding of a semaphorin to a cellular receptor.
12 . A method of diagnosing a patient for a predisposition to neurological disease associated with a genetic locus, said method comprising the steps of:
isolating somatic cells from a patient; isolating genomic DNA from said somatic cells; contacting said genomic DNA with a with a probe comprising a DNA sequence encoding a peptide according to claim 1 under conditions wherein said probe hybridizes to homologous DNA; identifying a region of said genomic DNA which hybridizes with said probe; wherein the presence, absence or sequence of said region correlates with a predisposition to a neurological disease.
14 . A method of treating a patient with neurological injury or disease or a pathological viral infection, said method comprising the steps of:
administering to a patient a therapeutically effective dosage of a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a peptide according to claim 1 ; wherein said peptide modulates neural cell growth cone function or viral pathogenicity in said patient.
15 . An isolated polypeptide comprising an amino acid sequence substantially similar to that of a semaphorin, and said polypeptide has a semaphorin binding specificity.
16 . An isolated peptide of at least about 5 amino acids comprising a unique portion of a semaphorin receptor, and said peptide has a semaphorin receptor binding specificity.
17 . An isolated antibody that specifically binds a peptide according to claim 16 .Join the waitlist — get patent alerts
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