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US4261886A Expired / Lapsed US ⏱️ 0.0 years remaining

Peptides having thymopoietin-like activity

Assignee: Ortho Pharmaceutical Corp
•
Filing: 1980-03-13
•
Granted: 1981-04-14
•
Expires: 2000-03-13
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Abstract

Abstract There are disclosed peptides having the following formula: 1 2 A-X-Z-Y-B wherein A is ##STR1## X is a suitable neutral, aliphatic or aromatic amino acid residue; e.g., one selected from the group consisting of ALA, 2-Me-ALA, GLY, LEU, ILE, LYS, THR, SER, PHE, MET, D-ALA, D-LEU, D-ILE, D-LYS, D-THR, allo-THR, D-SER, D-PHE, D-MET, and SAR; Z is ##STR2## Y is GLY, SER, THR, LEU, ILE, VAl, or SAR; B is TYR-R', D-TYR-R', decarboxy-TYR, or ##STR3## m is 3 or 4; n is 1, 2, or 3; R''' is hydrogen, C 1 -C 7 alkyl, C 6 -C 12 aryl, or C 1 -C 7 alkanoyl; and R and R' are substituents which do not substantially affect the biological activity of the peptides, provided that R-ARG-LYS-ASP-VAL-TYR-R' is excluded. These peptides have the capability of inducing the differentiation of T-lymphocytes but not of complement receptor (CR + ) B-lymphocytes and thus are useful in a number of therapeutic areas. Also provided are derivatives of the peptides, therapeutic compositions, and methods for use of the compositions.

Inventors

  • 👤 Gideon Goldstein
  • 👤 George Heavner

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-11-07 12:52
CPC Classifications
C; C07; C07K; C07K14/00; C07K14/435; C07K14/575; C07K14/66; C07K14/662; A; A61; A61K; A61K38/00; Y; Y10; Y10S; Y10S930/00; Y10S930/01; Y10S930/18

Claims Analysis

Total Claims: 38
Claim 1
Independent Claim 253 words
A peptide having the biological capability of inducing the differentiation of T-lymphocytes but not of complement receptor (CR + ) B lymphocytes, said peptide having the following sequence: A-X-Z-Y-B and the pharmaceutically acceptable salts thereof, wherein A is ##STR18## X is a suitable neutral, aliphatic or aromatic amino acid residue; e.g., one selected from the group consisting of ALA, 2-Me-ALA, GLY, LEU, ILE, LYS, THR, SER, PHE, MET, D-ALA, D-LEU, D-ILE, D-LYS, D-THR, allo-THR, D-SER, D-PHE, D-MET, and SAR; Z is ##STR19## Y is GLY, SER, THR, LEU, ILE, VAL, or SAR; B is TYR-R', D-TYR-R', decarboxy-TYR, or ##STR20## m is 3 or 4; n is 1, 2, or 3; R''' is hydrogen, C 1 -C 7 alkyl, C 6 -C 12 aryl, or C 1 -C 7 alkanoyl; R and R' are terminal groups on said peptide which do not substantially affect the biological capability thereof, said R and R' being selected from the groups consisting of: ______________________________________ R R' ______________________________________ Hydrogen OH C.sub.1 -C.sub.7 alkyl NH.sub.2 C.sub.6 -C.sub.12 aryl NHR" C.sub.6 -C.sub.20 alkaryl N(R").sub.2 C.sub.6 -C.sub.20 aralkyl OR" C.sub.1 -C.sub.7 alkanoyl -- C.sub.2 -C.sub.7 alkenyl VAL C.sub.2 -C.sub.7 alkynyl GLN GLN LEU GLU TYR GLY VAL--GLN GLU--GLN VAL--LEU GLY--GLN VAL--TYR GLY--GLU GLN--LEU GLY--GLU--GLN GLN--TYR GLN--VAL LEU--TYR LEU--LEU TYR--LEU VAL--GLN--LEU VAL--GLN--LEU--TYR VAL--GLN--LEU--TYR--LEU ______________________________________ wherein R" is C 1 -C 7 alkyl, C 2 -C 7 alkenyl, C 2 -C 7 alkynyl, C 6 -C 20 aryl, C 6 -C 20 aralkyl, or C 6 -C 20 alkaryl; provided that R-ARG-LYS-ASP-VAL-TYR-R' is excluded.
Claim 2
Dependent Claim 253 words
A peptide having the biological capability of inducing the differentiation of T-lymphocytes but not of complement receptor (CR + ) B lymphocytes, said peptide having the following sequence: A-X-Z-Y-B and the pharmaceutically acceptable salts thereof, wherein A is ##STR18## X is a suitable neutral, aliphatic or aromatic amino acid residue; e.g., one selected from the group consisting of ALA, 2-Me-ALA, GLY, LEU, ILE, LYS, THR, SER, PHE, MET, D-ALA, D-LEU, D-ILE, D-LYS, D-THR, allo-THR, D-SER, D-PHE, D-MET, and SAR; Z is ##STR19## Y is GLY, SER, THR, LEU, ILE, VAL, or SAR; B is TYR-R', D-TYR-R', decarboxy-TYR, or ##STR20## m is 3 or 4; n is 1, 2, or 3; R''' is hydrogen, C 1 -C 7 alkyl, C 6 -C 12 aryl, or C 1 -C 7 alkanoyl; R and R' are terminal groups on said peptide which do not substantially affect the biological capability thereof, said R and R' being selected from the groups consisting of: ______________________________________ R R' ______________________________________ Hydrogen OH C.sub.1 -C.sub.7 alkyl NH.sub.2 C.sub.6 -C.sub.12 aryl NHR" C.sub.6 -C.sub.20 alkaryl N(R").sub.2 C.sub.6 -C.sub.20 aralkyl OR" C.sub.1 -C.sub.7 alkanoyl -- C.sub.2 -C.sub.7 alkenyl VAL C.sub.2 -C.sub.7 alkynyl GLN GLN LEU GLU TYR GLY VAL--GLN GLU--GLN VAL--LEU GLY--GLN VAL--TYR GLY--GLU GLN--LEU GLY--GLU--GLN GLN--TYR GLN--VAL LEU--TYR LEU--LEU TYR--LEU VAL--GLN--LEU VAL--GLN--LEU--TYR VAL--GLN--LEU--TYR--LEU ______________________________________ wherein R" is C 1 -C 7 alkyl, C 2 -C 7 alkenyl, C 2 -C 7 alkynyl, C 6 -C 20 aryl, C 6 -C 20 aralkyl, or C 6 -C 20 alkaryl; provided that R-ARG-LYS-ASP-VAL-TYR-R' is excluded.
Claim 3
Dependent Claim 15 words
The peptide of claim 1 wherein m is 3 and n is 1 or 2.
Claim 4
Dependent Claim 15 words
The peptide of claim 2 wherein Z is ASP and Y is VAL or SAR.
Claim 5
Dependent Claim 13 words
The peptide of claim 3 wherein A is R-ARG and B is TYR-R'.
Claim 6
Dependent Claim 13 words
The peptide of claim 4 wherein X is SAR if Y is SAR.
Claim 7
Dependent Claim 14 words
A peptide according to claim 4 wherein R is hydrogen and R' is OH.
Claim 8
Dependent Claim 16 words
A peptide according to claim 4 wherein R is CH 3 CO-- and R' is OH.
Claim 9
Dependent Claim 15 words
A peptide according to claim 4 wherein R is CH 3 and R' is OH.
Claim 10
Dependent Claim 16 words
A peptide according to claim 4 wherein R is H and R' is --NH 2 .
Claim 11
Dependent Claim 16 words
A peptide according to claim 4 wherein R is H and R' is --NH(CH 3 ).
Claim 12
Dependent Claim 20 words
A peptide according to claim 4 wherein R is H and R' is --N(C 2 H 5 ) 2 .
Claim 13
Dependent Claim 18 words
A peptide according to claim 4 wherein R is CH 3 CO-- and R' is NH 2 .
Claim 14
Dependent Claim 16 words
A peptide according to claim 4 wherein R is H and R' is --OCH 3 .
Claim 15
Dependent Claim 18 words
A peptide according to claim 4 wherein R is H and R' is OC 2 H 5 .
Claim 16
Dependent Claim 14 words
A peptide according to claim 4 wherein R is phenyl and R' is --OH.
Claim 17
Dependent Claim 14 words
A peptide according to claim 4 wherein R is benzyl and R' is --OH.
Claim 18
Dependent Claim 14 words
A peptide according to claim 4 wherein R is tolyl- and R' is --OH.
Claim 19
Dependent Claim 14 words
A peptide according to claim 4 wherein R is GLN and R' is --OH.
Claim 20
Dependent Claim 14 words
A peptide according to claim 4 wherein R is GLU and R' is --OH.
Claim 21
Dependent Claim 14 words
A peptide according to claim 4 wherein R is GLY and R' is --OH.
Claim 22
Dependent Claim 14 words
A peptide according to claim 4 wherein R is H and R' is VAL.
Claim 23
Dependent Claim 14 words
A peptide according to claim 4 wherein R is H and R' is GLN.
Claim 24
Dependent Claim 14 words
A peptide according to claim 4 wherein R is H and R' is LEU.
Claim 25
Dependent Claim 14 words
A peptide according to claim 4 wherein R is H and R' is TYR.
Claim 26
Dependent Claim 14 words
A peptide according to claim 4 wherein R is H and R' is VAL-GLN.
Claim 27
Dependent Claim 14 words
A peptide according to claim 4 wherein R is GLN and R' is VAL.
Claim 28
Dependent Claim 14 words
A peptide according to claim 4 wherein R is GLU-GLN and R' is VAL-GLN.
Claim 29
Dependent Claim 13 words
A pentapeptide of the following sequence: H-ARG-SAR-ASP-VAL-TYR-NH.sub.2 and the pharmaceutically acceptable salts thereof.
Claim 30
Dependent Claim 13 words
A pentapeptide of the following sequence: H-ARG-SAR-ASP-VAL-TYR-NH.sub.2 and the pharmaceutically acceptable salts thereof.
Claim 31
Dependent Claim 13 words
A pentapeptide of the following sequence: H-ARG-D-ALA-ASP-VAL-TYR-NH.sub.2 and the pharmaceutically acceptable salts thereof.
Claim 32
Dependent Claim 13 words
A pentapeptide of the following sequence: H-ARG-D-ALA-ASP-VAL-TYR-NH.sub.2 and the pharmaceutically acceptable salts thereof.
Claim 33
Dependent Claim 13 words
A pentapeptide of the following sequence: H-ARG-SAR-ASP-SAR-TYR-NH.sub.2 and the pharmaceutically acceptable salts thereof.
Claim 34
Dependent Claim 13 words
A pentapeptide of the following sequence: H-ARG-SAR-ASP-SAR-TYR-NH.sub.2 and the pharmaceutically acceptable salts thereof.
Claim 35
Dependent Claim 38 words
A peptide of formula: A-SAR-ASP-Y-B wherein A is deamino ARG or H-ARG; Y is VAL or SAR; B is decarboxy-TYR, TYR-R', or ##STR21## and R' is H, OH, or NH 2 ; and the pharmaceutically acceptable salts thereof.
Claim 36
Dependent Claim 38 words
A peptide of formula: A-SAR-ASP-Y-B wherein A is deamino ARG or H-ARG; Y is VAL or SAR; B is decarboxy-TYR, TYR-R', or ##STR21## and R' is H, OH, or NH 2 ; and the pharmaceutically acceptable salts thereof.
Claim 37
Dependent Claim 9 words
The peptide of claim 31 wherein Y is SAR.
Claim 38
Dependent Claim 11 words
The peptide of claim 32 wherein B is TYR-NH 2 .

References Cited (Backward Citations)

US4079127A Cited

USPTO Annuity & Maintenance Windows

Annuity Stage Window Opens Payment Deadline Surcharge Period Until Estimated Fee Status
3.5 Years (Year 4) 1984-04-13 1984-10-13 1985-04-14 $2000.00 Window Closed / Lapsed
7.5 Years (Year 8) 1988-04-13 1988-10-13 1989-04-14 $3760.00 Window Closed / Lapsed
11.5 Years (Year 12) 1992-04-13 1992-10-13 1993-04-14 $7700.00 Window Closed / Lapsed

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