US4190647A
Expired / Lapsed
US
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Polypeptides and methods
Assignee: Memorial Sloan Kettering Cancer Center
•
Filing: 1979-01-26
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Granted: 1980-02-26
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Expires: 1999-01-26
Abstract
Abstract There are disclosed new polypeptide compositions having the following amino acid sequence as the active site: TYR-ASN-ILE-GLN-LYS This polypeptide has the capability of inducing the differentiation of both T-precursor cells as measured by the acquisition of the thymic differentiation antigens TL and THY-1 (θ), as well as B-precursor cells as measured by the acquisition of receptors for complement, a distinctive marker of B cells. The peptide is thus useful in thymic function and immunity areas such as in treatment for a congenital absence of thymus. The peptide is active in very low concentrations. Also provided are derivatives of the pentapeptide, novel intermediate polypeptides, methods of manufacture of the peptides, therapeutic compositions, and methods for use of the compositions.
Inventors
- 👤 Gideon Goldstein
- 👤 David H. Schlesinger
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-29 14:44
CPC Classifications
C; C07; C07K; C07K7/00; C07K7/04; C07K7/06; C07K14/00; C07K14/435; C07K14/575; A; A61; A61K; A61K38/00
Claims Analysis
Total Claims: 35
Claim 1
Independent Claim
175 words
A polypeptide having the biological capability of inducing the differentiation of both T-lymphocytes and of complement receptor (CR + ) B-lymphocytes, said polypeptide having the following sequence: R-NH-X-Y-Z-GLN-LYS-COR' X is TYR or ALA, Y is ASN is ALA, and Z is ILE or ALA, and R and R' are terminal groups on said polypeptide which do not substantially affect the biological capability thereof, and the pharmaceutically acceptable salts, wherein R and R' are selected from the groups consisting of: ______________________________________
R R'
______________________________________
Hydrogen OH
C.sub.1 -C.sub.7 alkyl
NH.sub.2
C.sub.5 -C.sub.12 aryl
NHR.sub.7
C.sub.6 -C.sub.20 alkaryl
N(R.sub.7).sub.2
C.sub.6 -C.sub.20 aralkyl
OR.sub.7
C.sub.1 -C.sub.7 alkanoyl
GLU
C.sub.2 -C.sub.7 alkenyl
SER
C.sub.2 -C.sub.7 alkynyl
THR
ASP LEU
SER HIS
LEU VAL
SER-ASP ARG
LEU-SER ASP GLU-SER
LEU-ASP GLU-THR
LEU-SER
R'
______________________________________
GLU-SER-LEU
GLU-SER-THR
GLU-SER-THR-LEU
GLU-SER-THR-LEU-HIS
GLU-SER-THR-LEU-HIS-LEU
GLU-SER-THR-LEU-HIS-LEU-VAL
GLU-SER-THR-LEU-HIS-LEU-VAL-LEU
GLU-SER-THR-LEU-HIS-LEU-VAL-LEU-ARG
GLU-SER-THR-LEU-HIS-LEU-VAL-LEU-ARG-LEU
GLU-SER-THR-LEU-HIS-LEU-VAL-LEU-ARG-LEU-ARG
______________________________________ wherein R 7 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.
Claim 2
Dependent Claim
175 words
A polypeptide having the biological capability of inducing the differentiation of both T-lymphocytes and of complement receptor (CR + ) B-lymphocytes, said polypeptide having the following sequence: R-NH-X-Y-Z-GLN-LYS-COR' X is TYR or ALA, Y is ASN is ALA, and Z is ILE or ALA, and R and R' are terminal groups on said polypeptide which do not substantially affect the biological capability thereof, and the pharmaceutically acceptable salts, wherein R and R' are selected from the groups consisting of: ______________________________________
R R'
______________________________________
Hydrogen OH
C.sub.1 -C.sub.7 alkyl
NH.sub.2
C.sub.5 -C.sub.12 aryl
NHR.sub.7
C.sub.6 -C.sub.20 alkaryl
N(R.sub.7).sub.2
C.sub.6 -C.sub.20 aralkyl
OR.sub.7
C.sub.1 -C.sub.7 alkanoyl
GLU
C.sub.2 -C.sub.7 alkenyl
SER
C.sub.2 -C.sub.7 alkynyl
THR
ASP LEU
SER HIS
LEU VAL
SER-ASP ARG
LEU-SER ASP GLU-SER
LEU-ASP GLU-THR
LEU-SER
R'
______________________________________
GLU-SER-LEU
GLU-SER-THR
GLU-SER-THR-LEU
GLU-SER-THR-LEU-HIS
GLU-SER-THR-LEU-HIS-LEU
GLU-SER-THR-LEU-HIS-LEU-VAL
GLU-SER-THR-LEU-HIS-LEU-VAL-LEU
GLU-SER-THR-LEU-HIS-LEU-VAL-LEU-ARG
GLU-SER-THR-LEU-HIS-LEU-VAL-LEU-ARG-LEU
GLU-SER-THR-LEU-HIS-LEU-VAL-LEU-ARG-LEU-ARG
______________________________________ wherein R 7 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.
Claim 3
Dependent Claim
48 words
A pentapeptide of the following sequence: R-HN-TYR-ASN-ILE-GLN-LYS-COR' wherein R is hydrogen, C 1 -C 7 alkyl, C 5 -C 12 aryl, or C 1 -C 7 alkanoyl, and R' is OH, NH 2 , NHR 7 , or N(R 7 ) 2 , and the pharmaceutically acceptable salts.
Claim 4
Dependent Claim
48 words
A pentapeptide of the following sequence: R-HN-TYR-ASN-ILE-GLN-LYS-COR' wherein R is hydrogen, C 1 -C 7 alkyl, C 5 -C 12 aryl, or C 1 -C 7 alkanoyl, and R' is OH, NH 2 , NHR 7 , or N(R 7 ) 2 , and the pharmaceutically acceptable salts.
Claim 5
Dependent Claim
13 words
A polypeptide of the following sequence: H.sub.2 N-TYR-ASN-ILE-GLN-LYS-COOH and the pharmaceutically acceptable salts.
Claim 6
Dependent Claim
13 words
A polypeptide of the following sequence: H.sub.2 N-TYR-ASN-ILE-GLN-LYS-COOH and the pharmaceutically acceptable salts.
Claim 7
Dependent Claim
14 words
A polypeptide according to claim 1 wherein R is hydrogen and R' is OH.
Claim 8
Dependent Claim
16 words
A polypeptide according to claim 1 wherein R is CH 3 CO-- and R' is OH.
Claim 9
Dependent Claim
15 words
A polypeptide according to claim 1 wherein R is CH 3 and R' is OH.
Claim 10
Dependent Claim
16 words
A polypeptide according to claim 1 wherein R is H and R' is NH 2 .
Claim 11
Dependent Claim
20 words
A polypeptide according to claim 1 wherein R is H and R' is N(C 2 H 5 ) 2 .
Claim 12
Dependent Claim
18 words
A polypeptide according to claim 1 wherein R is CH 3 CO-- and R' is NH 2 .
Claim 13
Dependent Claim
16 words
A polypeptide according to claim 1 wherein R is H and R' is --OCH 3 .
Claim 14
Dependent Claim
18 words
A polypeptide according to claim 1 wherein R is H and R' is OC 2 H 5 .
Claim 15
Dependent Claim
21 words
A polypeptide according to claim 1 wherein R is C 2 H 5 and R' is OC 2 H 5 .
Claim 16
Dependent Claim
17 words
A polypeptide according to claim 1 wherein R is CH 3 and R' is --NH 2 .
Claim 17
Dependent Claim
14 words
A polypeptide according to claim 1 wherein R is ASP and R' is --OH.
Claim 18
Dependent Claim
14 words
A polypeptide according to claim 1 wherein R is SER-ASP and R' is --OH.
Claim 19
Dependent Claim
14 words
A polypeptide according to claim 1 wherein R is LEU-SER-ASP and R' is --OH.
Claim 20
Dependent Claim
14 words
A polypeptide according to claim 1 wherein R is LEU-SER-ASP and R' is GLU.
Claim 21
Dependent Claim
14 words
A polypeptide according to claim 1 wherein R is LEU-SER-ASP and R' is GLU-SER.
Claim 22
Dependent Claim
14 words
A polypeptide according to claim 1 wherein R is LEU-SER-ASP and R' is GLU-SER-THR.
Claim 23
Dependent Claim
14 words
A polypeptide according to claim 1 wherein R is LEU-SER-ASP and R' is GLU-SER-THR-LEU.
Claim 24
Dependent Claim
14 words
A polypeptide according to claim 1 wherein R is LEU-SER-ASP and R' is GLU-SER-THR-LEU-HIS.
Claim 25
Dependent Claim
14 words
A polypeptide according to claim 1 wherein R is ASP and R' is GLU.
Claim 26
Dependent Claim
14 words
A polypeptide according to claim 1 wherein R is ASP and R' is GLU-SER.
Claim 27
Dependent Claim
14 words
A polypeptide according to claim 1 wherein R is hydrogen and R' is GLU-SER-THR-LEU-HIS-LEU-VAL-LEU-ARG-LEU-ARG.
Claim 28
Dependent Claim
21 words
A therapeutic composition of matter comprising a therapeutically effective amount of the polypeptide of claim 1 in a pharmaceutically acceptable carrier.
Claim 29
Dependent Claim
24 words
A therapeutic composition of matter according to claim 25 wherein the therapeutically effective amount of the polypeptide ranges from about 0.1 to 10 mg/kg.
Claim 30
Dependent Claim
29 words
A method for the treatment of conditions resulting from relative or absolute T cell deficiencies which comprises administration of a therapeutically effective amount of the polypeptide of claim 1.
Claim 31
Dependent Claim
29 words
A method for the treatment of conditions resulting from relative or absolute B cell deficiencies which comprises administration of a therapeutically effective amount of the polypeptide of claim 1.
Claim 32
Dependent Claim
28 words
A method for inducing bone marrow cells to develop the characteristics of thymus-derived lymphocytes which comprises administration of a therapeutically effective amount of the polypeptide of claim 1.
Claim 33
Dependent Claim
29 words
A method for inducing bone marrow cells to develop the characteristics of immuno-competent B cells which comprises administration of a therapeutically effective amount of the polypeptide of claim 1.
Claim 34
Dependent Claim
37 words
A method for affecting the immune response in the body to assist in the correction of relative or absolute deficiencies of the thymus which comprises administration of a therapeutically effective amount of the polypeptide of claim 1.
Claim 35
Dependent Claim
42 words
A method for affecting the immune response in the body to assist in the correction of relative or absolute deficiencies of the body tissues which differentiate B cells which comprises administration of a therapeutically effective amount of the polypeptide of claim 1.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1983-02-25 | 1983-08-27 | 1984-02-26 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1987-02-25 | 1987-08-27 | 1988-02-26 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1991-02-25 | 1991-08-27 | 1992-02-26 | $7700.00 | Window Closed / Lapsed |