US2009054344A1PendingUtilityA1
Anti-angiogenic proteins and fragments and methods of use thereof
Est. expiryJun 17, 2018(expired)· nominal 20-yr term from priority
Inventors:Raghuram Kalluri
A61P 35/00C07K 14/78C07K 14/7055C07K 16/2839A61P 31/00A61K 38/00A61K 2039/505A61K 38/16
53
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Claims
Abstract
Proteins with anti-angiogenic properties are disclosed, and fragments thereof, and methods of using those proteins and fragments to inhibit or promote angiogenesis.
Claims
exact text as granted — not AI-modified1 . An isolated peptide of the formula: R 1 X 1 LFX 2 NVNX 3 VX 4 NFR 2 (SEQ ID NO: 45), wherein R1 is hydrogen or a peptidyl chain of 1 to 17 amino acids, R2 is hydrogen or a peptidyl chain of 1 to 12 amino acids, and X1, X2 and X3 are individually an amino acid, and wherein said peptide inhibits tumor growth.
2 . The isolated peptide of claim 1 , wherein X1 is an amino acid with a basic side chain or an amino acid with an aromatic side chain.
3 . The isolated peptide of claim 2 , wherein X1 is phenylalanaine, tyrosine, tryptophan, lysine, arginine, histidine, glutamine or asparagine.
4 . The isolated peptide of claim 3 , wherein X1 is lysine or phenylalanine.
5 . The isolated peptide of claim 1 , wherein X2, X3 and X4 are independently an amino acid with a hydrophilic side chain or an amino acid with a basic side chain.
6 . The isolated peptide of claim 5 , wherein X2, X3 and X4 are independently cysteine, serine, threonine, aspartic acid or glutamine.
7 . The isolated peptide of claim 6 , wherein X2 and X4 are independently cysteine, serine or aspartic acid and X3 is cysteine or aspartic acid.
8 . The isolated peptide of claim 1 , wherein X1 is phenylalanine, tyrosine, tryptophan, lysine, arginine, histidine, glutamine or asparagine and X2, X3 and X4 are independently cysteine, serine, threonine, aspartic acid or glutamine.
9 . The isolated peptide of claim 1 , wherein R1 is one amino acid or a peptidyl chain of 2, 3, 4, 5, 6, 7, or 8 amino acid residues.
10 . The isolated peptide of claim 9 , wherein said amino acid or peptidyl chain represented by R1 is selected from the group consisting of:
(a)
P;
(b)
MP;
(c)
TMP;
(d)
TTMP;
(SEQ ID NO: 46)
(e)
FTTMP;
(SEQ ID NO: 47)
(f)
RFTTMP;
(SEQ ID NO: 48)
(g)
QRFTTMP;
(SEQ ID NO: 49)
(h)
LQRFTTMP;
(SEQ ID NO: 50)
(i)
KQRFTTMP;
(SEQ ID NO: 51)
and
(j)
a conservative variant of
any of (a)-(i).
11 . The isolated peptide of claim 1 , wherein R2 is one amino acid or a peptidyl chain of 2, 3, 4, 5, 6, 7, 8, or 9 amino acid residues.
12 . The isolated peptide of claim 11 , wherein said amino acid or peptidyl chain represented by R2 is selected from the group consisting of:
(a)
A;
(b)
AS;
(c)
ASR;
(d)
ASRN;
(SEQ ID NO: 52)
(e)
ASRND;
(SEQ ID NO: 53)
(f)
ASRNDY;
(SEQ ID NO: 54)
(g)
ASRNDYS;
(SEQ ID NO: 55)
(h)
ASRNDYSY;
(SEQ ID NO: 56)
(i)
ASRNDYSYW;
(SEQ ID NO: 57)
(j)
ASRNDYSYWL;
(SEQ ID NO: 58)
and
(k)
a conservative variant of any of
(a)-(j).
13 . The isolated peptide of claim 1 , wherein the peptide is reduced.
14 . The isolated peptide of claim 1 , wherein the peptide is alkylated.
15 . The isolated peptide of claim 1 , wherein the peptide is oxidized.
16 . An isolated peptide of the formula: R 1 X 1 LFX 2 NVNX 3 VX 4 NFR 2 (SEQ ID NO: 45), wherein R1 is hydrogen or a peptidyl chain of 1 to 17 amino acids, R2 is hydrogen or a peptidyl chain of 1 to 12 amino acids, and X1, X2 and X3 are individually an amino acid, and wherein said peptide inhibits angiogenic activity in mammalian tissue.
17 . The isolated peptide of claim 16 , wherein X1 is an amino acid with a basic side chain or an amino acid with an aromatic side chain.
18 . The isolated peptide of claim 17 , wherein X1 is phenylalanaine, tyrosine, tryptophan, lysine, arginine, histidine, glutamine or asparagine.
19 . The isolated peptide of claim 18 , wherein X1 is lysine or phenylalanine.
20 . The isolated peptide of claim 16 , wherein X2, X3 and X4 are independently an amino acid with a hydrophilic side chain or an amino acid with a basic side chain.
21 . The isolated peptide of claim 20 , wherein X2, X3 and X4 are independently cysteine, serine, threonine, aspartic acid or glutamine.
22 . The isolated peptide of claim 21 , wherein X2 and X4 are independently cysteine, serine or aspartic acid and X3 is cysteine or aspartic acid.
23 . The isolated peptide of claim 16 , wherein X1 is phenylalanine, tyrosine, tryptophan, lysine, arginine, histidine, glutamine or asparagine and X2, X3 and X4 are independently cysteine, serine, threonine, aspartic acid or glutamine.
24 . The isolated peptide of claim 16 , wherein R1 is one amino acid or a peptidyl chain of 2, 3, 4, 5, 6, 7, or 8 amino acid residues.
25 . The isolated peptide of claim 24 , wherein said amino acid or peptidyl chain represented by R1 is selected from the group consisting of:
(a)
P;
(b)
MP;
(c)
TMP;
(d)
TTMP;
(SEQ ID NO: 46)
(e)
FTTMP;
(SEQ ID NO: 47)
(f)
RFTTMP;
(SEQ ID NO: 48)
(g)
QRFTTMP;
(SEQ ID NO: 49)
(h)
LQRFTTMP;
(SEQ ID NO: 50)
(i)
KQRFTTMP;
(SEQ ID NO: 51)
and
(j)
a conservative variant of any of
(a)-(i).
26 . The isolated peptide of claim 16 , wherein R2 is one amino acid or a peptidyl chain of 2, 3, 4, 5, 6, 7, 8, or 9 amino acid residues.
27 . The isolated peptide of claim 26 , wherein said amino acid or peptidyl chain represented by R2 is selected from the group consisting of:
(a)
A;
(b)
AS;
(c)
ASR;
(d)
ASRN;
(SEQ ID NO: 52)
(e)
ASRND;
(SEQ ID NO: 53)
(f)
ASRNDY;
(SEQ ID NO: 54)
(g)
ASRNDYS;
(SEQ ID NO: 55)
(h)
ASRNDYSY;
(SEQ ID NO-56)
(i)
ASRNDYSYW;
(SEQ ID NO: 57)
(j)
ASRNDYSYWL;
(SEQ ID NO: 58)
and
(k)
a conservative variant of any of
(a)-(j).
28 . The isolated peptide of claim 16 , wherein the peptide is reduced.
29 . The isolated peptide of claim 16 , wherein the peptide is alkylated.
30 . The isolated peptide of claim 16 , wherein the peptide is oxidized.
31 . An isolated peptide of the formula: R 1 X 1 LFX 2 NVNX 3 VX 4 NFR 2 (SEQ ID NO: 45), wherein R1 is hydrogen or a peptidyl chain of 1 to 17 amino acids, R2 is hydrogen or a peptidyl chain of 1 to 12 amino acids, and X1, X2 and X3 are individually an amino acid, and wherein said peptide inhibits protein synthesis in endothelial cells.
32 . The isolated peptide of claim 31 , wherein Xi vis an amino acid with a basic side chain or an amino acid with an aromatic side chain.
33 . The isolated peptide of claim 32 , wherein X1 is phenylalanaine, tyrosine, tryptophan, lysine, arginine, histidine, glutamine or asparagine.
34 . The isolated peptide of claim 33 , wherein Xi is lysine or phenylalanine.
35 . The isolated peptide of claim 31 , wherein X2, X3 and X4 are independently an amino acid with a hydrophilic side chain or an amino acid with a basic side chain.
36 . The isolated peptide of claim 35 , wherein X2, X3 and X4 are independently cysteine, serine, threonine, aspartic acid or glutamine.
37 . The isolated peptide of claim 36 , wherein X2 and X4 are independently cysteine, serine or aspartic acid and X3 is cysteine or aspartic acid.
38 . The isolated peptide of claim 31 , wherein X1 is phenylalanine, tyrosine, tryptophan, lysine, arginine, histidine, glutamine or asparagine and X2, X3 and X4 are independently cysteine, serine, threonine, aspartic acid or glutamine.
39 . The isolated peptide of claim 31 , wherein R1 is one amino acid or a peptidyl chain of 2, 3, 4, 5, 6, 7, or 8 amino acid residues.
40 . The isolated peptide of claim 39 , wherein said amino acid or peptidyl chain represented by R′ is selected from the group consisting of:
(a)
P;
(b)
MP;
(c)
TMP;
(d)
TTMP;
(SEQ ID NO: 46)
(e)
FTTMP;
(SEQ ID NO: 47)
(f)
RFTTMP;
(SEQ ID NO: 48)
(g)
QRFTTMP;
(SEQ ID NO: 49)
(h)
LQRFTTMP;
(SEQ ID NO: 50)
(i)
KQRFTTMP;
(SEQ ID NO: 51)
and
(j)
a conservative variant of any of
(a)-(i).
41 . The isolated peptide of claim 31 , wherein R2 is one amino acid or a peptidyl chain of 2, 3, 4, 5, 6, 7, 8, or 9 amino acid residues.
42 . The isolated peptide of claim 41 , wherein said amino acid or peptidyl chain represented by R2 is selected from the group consisting of:
(a)
A;
(b)
AS;
(c)
ASR;
(d)
ASRN;
(SEQ ID NO: 52)
(e)
ASRND;
(SEQ ID NO: 53)
(f)
ASRNDY;
(SEQ ID NO: 54)
(g)
ASRNDYS;
(SEQ ID NO: 55)
(h)
ASRNDYSY;
(SEQ ID NO: 56)
(i)
ASRNDYSYW;
(SEQ ID NO: 57)
(j)
ASRNDYSYWL;
(SEQ ID NO: 58)
and
(k)
a conservative variant of any of
(a)-(j).
43 . The isolated peptide of claim 31 , wherein the peptide is reduced, alkylated, or oxidized.
44 . A composition comprising the isolated peptide of claim 1 for use in inhibiting tumor growth in mammalian tissue.
45 . Use of a composition comprising the isolated peptide of claim 1 for the manufacture of a medicament for inhibiting tumour growth in mammalian tissue.
46 . Use of a composition comprising the isolated peptide of claim 16 for the manufacture of a medicament for inhibiting angiogenic activity in mammalian tissue.
47 . Use of a composition comprising the isolated peptide of claim 31 for the manufacture of a medicament for inhibiting protein synthesis.
48 . The isolated peptide of claim 1 , combined with a pharmaceutically-acceptable carrier.
49 . The isolated peptide of claim 16 , combined with a pharmaceutically-acceptable carrier.
50 . The isolated peptide of claim 31 , combined with a pharmaceutically-acceptable carrier.
51 . An isolated fragment of SEQ ID NO: 10, having the ability to inhibit tumor growth.
52 . The isolated fragment of claim 51 , wherein the fragment is SEQ ID NO: 37.
53 . The isolated fragment of claim 51 , wherein the fragment is reduced, alkylated, or oxidized.Join the waitlist — get patent alerts
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