Patent EP0226397A2 successfully refreshed from Google Patents.
US4232008A
Expired / Lapsed
US
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Tetrapeptides and methods
Assignee: Ortho Pharmaceutical Corp
•
Filing: 1978-11-17
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Granted: 1980-11-04
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Expires: 1998-11-17
Abstract
Abstract There are disclosed new biologically active polypeptides containing the following polypeptide segment: --ALA--LYS--SER--GLN-- Biological activity is generally retained upon substitution of a natural or non-natural amino acid residue for either or both of L-alanyl in the first position and L-seryl in the third position. These polypeptides have the capability of inducing the differentiation of T-lymphocytes as measured by the acquisition of the thymic differentiation antigen Th-1, as well as B-lymphocytes as measured by the acquisition of the differentiation antigen Bu-1. The polypeptides are thus useful in thymic function and immunity areas such as in treatment for congenital absence of thymus. Also provided are substituted polypeptides, methods of manufacture of the polypeptides, therapeutic compositions, and methods for use of the polypeptides.
Inventors
- 👤 Gideon Goldstein
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-29 18:41
CPC Classifications
C; C07; C07K; C07K7/00; C07K7/04; C07K7/06; C07K5/00; C07K5/04; C07K5/10; C07K5/1002; C07K5/1005; C07K5/1008; C07K5/1021; C07K7/062; A; A61; A61K; A61K38/00; Y; Y10; Y10S; Y10S930/00; Y10S930/01; Y10S930/18
Claims Analysis
Total Claims: 42
Claim 1
Independent Claim
193 words
A polypeptide having the capability of inducing the differentiation of both Th-1 + T-lymphocytes and Bu-1 + B-lymphocytes, said polypeptide having the following sequence: R--X--LYS--Y--GLN--R' wherein X and Y are each natural and non-natural amino acid residues selected from the group consisting of L-asparagyl, L-glutamyl, L-threonyl, glycyl, L-valyl, L-leucyl, L-alanyl, L-seryl, sarcosyl, 2-methylalanyl, D-asparagyl, D-glutamyl, D-threonyl, D-valyl, D-leucyl, D-alanyl, and D-seryl and R and R' are each 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.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.2 -C.sub.7 alkanoyl
C.sub.2 -C.sub.7 alkenyl
GLY
C.sub.1 -C.sub.7 alkynyl
GLY-GLY
GLN
SAR GLY--GLY--SER--ASN
______________________________________ 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, and C 6 -C 20 alkaryl, provided that when R is GLN, R' is other than GLY--GLY--SER--ASN, and the pharmaceutically acceptable salts thereof; further provided that said polypeptide induce the differentiation of both Th-1 + T-lymphocytes and Bu-1 + B-lymphocytes in the chicken induction assay at a concentration of about one ng/ml or less.
Claim 2
Dependent Claim
193 words
A polypeptide having the capability of inducing the differentiation of both Th-1 + T-lymphocytes and Bu-1 + B-lymphocytes, said polypeptide having the following sequence: R--X--LYS--Y--GLN--R' wherein X and Y are each natural and non-natural amino acid residues selected from the group consisting of L-asparagyl, L-glutamyl, L-threonyl, glycyl, L-valyl, L-leucyl, L-alanyl, L-seryl, sarcosyl, 2-methylalanyl, D-asparagyl, D-glutamyl, D-threonyl, D-valyl, D-leucyl, D-alanyl, and D-seryl and R and R' are each 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.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.2 -C.sub.7 alkanoyl
C.sub.2 -C.sub.7 alkenyl
GLY
C.sub.1 -C.sub.7 alkynyl
GLY-GLY
GLN
SAR GLY--GLY--SER--ASN
______________________________________ 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, and C 6 -C 20 alkaryl, provided that when R is GLN, R' is other than GLY--GLY--SER--ASN, and the pharmaceutically acceptable salts thereof; further provided that said polypeptide induce the differentiation of both Th-1 + T-lymphocytes and Bu-1 + B-lymphocytes in the chicken induction assay at a concentration of about one ng/ml or less.
Claim 3
Dependent Claim
14 words
A polypeptide according to claim 1, wherein R is hydrogen and R' is OH.
Claim 4
Dependent Claim
16 words
A polypeptide according to claim 1, wherein R is CH 3 CO-- and R' is OH.
Claim 5
Dependent Claim
15 words
A polypeptide according to claim 1, wherein R is CH 3 and R' is OH.
Claim 6
Dependent Claim
16 words
A polypeptide according to claim 1, wherein R is H and R' is NH 2 .
Claim 7
Dependent Claim
14 words
A polypeptide according to claim 1, wherein R is H and R' is Cl.
Claim 8
Dependent Claim
20 words
A polypeptide according to claim 1, wherein R is H and R' is N(C 2 H 5 ) 2 .
Claim 9
Dependent Claim
18 words
A polypeptide according to claim 1, wherein R is CH 3 CO-- and R' is NH 2 .
Claim 10
Dependent Claim
16 words
A polypeptide according to claim 1, wherein R is H and R' is --OCH 3 .
Claim 11
Dependent Claim
18 words
A polypeptide according to claim 1, wherein R is H and R' is OC 2 H 5 .
Claim 12
Dependent Claim
14 words
A polypeptide according to claim 1, wherein R is phenyl and R' is --OH.
Claim 13
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 14
Dependent Claim
19 words
A polypeptide according to claim 1, wherein R is C 2 H 5 and R' is --NH 2 .
Claim 15
Dependent Claim
14 words
A polypeptide according to claim 1, wherein R is GLN and R' is --OH.
Claim 16
Dependent Claim
14 words
A polypeptide according to claim 1, wherein R is SAR and R' is --OH.
Claim 17
Dependent Claim
14 words
A polypeptide according to claim 1, wherein R is hydrogen and R' is GLY.
Claim 18
Dependent Claim
14 words
A polypeptide according to claim 1, wherein R is hydrogen and R' is GLY--GLY.
Claim 19
Dependent Claim
14 words
A polypeptide according to claim 1, wherein R is hydrogen and R' is GLY--GLY--SER--ASN.
Claim 20
Dependent Claim
14 words
A polypeptide according to claim 1, wherein R is GLN and R' is GLY.
Claim 21
Dependent Claim
14 words
A polypeptide according to claim 1, wherein R is GLN and R' is GLY--GLY.
Claim 22
Dependent Claim
14 words
A polypeptide according to claim 1, wherein R is SAR and R' is GLY.
Claim 23
Dependent Claim
14 words
A polypeptide according to claim 1, wherein R is SAR and R' is GLY--GLY.
Claim 24
Dependent Claim
14 words
A polypeptide according to claim 1, wherein R is SAR and R' is GLY--GLY--SER--ASN.
Claim 25
Dependent Claim
14 words
A polypeptide of the following sequence: H.sub.2 N--ALA--LYS--SER--GLN--COOH and the pharmaceutically acceptable salts thereof.
Claim 26
Dependent Claim
14 words
A polypeptide of the following sequence: H.sub.2 N--ALA--LYS--SER--GLN--COOH and the pharmaceutically acceptable salts thereof.
Claim 27
Dependent Claim
112 words
A polypeptide of the following sequence: R--X--LYS--Y--GLN--R' wherein X and Y are each selected from the group consisting of D-ALA and SAR and R and R' are each 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.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
C.sub.2 -C.sub.7 alkenyl
GLY
C.sub.2 -C.sub.7 alkynyl
GLY--GLY
GLN
SAR GLY--GLY--SER--ASN
______________________________________ 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, and C 6 --C 20 alkaryl, and the pharmaceutically acceptable salts thereof.
Claim 28
Dependent Claim
112 words
A polypeptide of the following sequence: R--X--LYS--Y--GLN--R' wherein X and Y are each selected from the group consisting of D-ALA and SAR and R and R' are each 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.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
C.sub.2 -C.sub.7 alkenyl
GLY
C.sub.2 -C.sub.7 alkynyl
GLY--GLY
GLN
SAR GLY--GLY--SER--ASN
______________________________________ 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, and C 6 --C 20 alkaryl, and the pharmaceutically acceptable salts thereof.
Claim 29
Dependent Claim
13 words
A polypeptide of the following sequence: H--SAR--LYS--SAR--GLN--NH.sub.2 and the pharmaceutically acceptable salts thereof.
Claim 30
Dependent Claim
13 words
A polypeptide of the following sequence: H--SAR--LYS--SAR--GLN--NH.sub.2 and the pharmaceutically acceptable salts thereof.
Claim 31
Dependent Claim
13 words
A polypeptide of the following sequence: H--SAR--LYS--D--ALA--GLN--NH.sub.2 and the pharmaceutically acceptable salts thereof.
Claim 32
Dependent Claim
13 words
A polypeptide of the following sequence: H--SAR--LYS--D--ALA--GLN--NH.sub.2 and the pharmaceutically acceptable salts thereof.
Claim 33
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 34
Dependent Claim
27 words
A therapeutic composition of matter according to claim 28, wherein the therapeutically effective amount of the polypeptide ranges from about 1 to about 100 μg/kg body weight.
Claim 35
Dependent Claim
21 words
A therapeutic composition of matter comprising a therapeutically effective amount of the polypeptide of claim 25 in a pharmaceutically acceptable carrier.
Claim 36
Dependent Claim
30 words
A therapeutic composition of matter comprising from about 0.1 ng/kg to about 10 μg/kg body weight of the polypeptide of claim 26 or claim 27 in a pharmaceutically acceptable carrier.
Claim 37
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 38
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 39
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 40
Dependent Claim
29 words
A method for inducing bone marrow cells to develop the characteristics of immunocompetent B cells which comprises administration of a therapeutically effective amount of the polypeptide of claim 1.
Claim 41
Dependent Claim
37 words
A method for affecting the immune response in the body to assist to 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 42
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) | 1983-11-04 | 1984-05-05 | 1984-11-04 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1987-11-04 | 1988-05-05 | 1988-11-04 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1991-11-04 | 1992-05-05 | 1992-11-04 | $7700.00 | Window Closed / Lapsed |