Patent US3963691A successfully refreshed from Google Patents.
US3963691A
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Synthetic antigens of luteinizing hormone releasing hormone
Assignee: Merck and Co Inc
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Filing: 1974-10-07
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Granted: 1976-06-15
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Expires: 1994-10-07
Abstract
Abstract Synthetic antigens related to luteinizing hormone-releasing hormone (hereinafter designated LH-RH) having the amino acid composition, pyroglutamyl-histidyl-tryptophanylseryl-tyrosyl-glycyl-leucyl-arginyl- prolyl-glycyl-poly-L-lysine (hereinafter designated pyroglu-his-trp-ser-tyr-glyleu-arg-pro-gly-poly-L-lys) and poly-L-lysyl-glutarylhistidyl-tryptophanyl-seryl-tyrosyl-glycyl-leucyl -arginylprolyl-glycine amide (hereinafter designated poly-L-lysglutaryl-his-trp-ser-tyr-gly-leu-arg-pro-gly) are prepared by coupling the corresponding decapeptide with poly-L-lysine. The corresponding decapeptides are prepared by controlled stepwise procedures starting with individual amino acid components. These antigens have the property of inducing formation of antibodies to luteinizing hormone-releasing hormone (LH-RH) in animals.
Inventors
- 👤 Carl H. Hoffman
- 👤 Harvey Schwam
- 👤 Stephen F. Brady
- 👤 Martin Hichens
- 👤 Ruth F. Nutt
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-29 17:21
CPC Classifications
C; C07; C07K; C07K5/00; C07K5/04; C07K5/08; C07K5/0821; C07K5/10; C07K5/1002; C07K5/1005; C07K7/00; C07K7/04; C07K7/23; A; A61; A61K; A61K39/00; Y; Y10; Y10S; Y10S530/00; Y10S530/81; Y10S530/812; Y10S530/815; Y10S930/00; Y10S930/01; Y10S930/13; Y10S930/28
Claims Analysis
Total Claims: 11
Claim 1
Independent Claim
58 words
The antigen 1-N.sup.α-glutaryl-LH-RH-[2-10]-carrier wherein the peptide 1-N.sup.α-glutaryl-LH-RH-[2-10], having the amino acid sequence glutaryl-his-trp-ser-tyr-gly-leu-arg-pro-gly-NH 2 , is linked to a carrier selected from the group consisting of α, β and γ globulins, thyroglobulins, Keyhole Limpet Hemocyanin, poly-L-glutamic acid, and poly-L-lysine by a peptide linkage between the carboxyl group of the glutaryl moiety and the amino groups of said carrier.
Claim 2
Dependent Claim
58 words
The antigen 1-N.sup.α-glutaryl-LH-RH-[2-10]-carrier wherein the peptide 1-N.sup.α-glutaryl-LH-RH-[2-10], having the amino acid sequence glutaryl-his-trp-ser-tyr-gly-leu-arg-pro-gly-NH 2 , is linked to a carrier selected from the group consisting of α, β and γ globulins, thyroglobulins, Keyhole Limpet Hemocyanin, poly-L-glutamic acid, and poly-L-lysine by a peptide linkage between the carboxyl group of the glutaryl moiety and the amino groups of said carrier.
Claim 3
Dependent Claim
33 words
The antigen 1-N.sup.α-glutaryl-LH-RH-[2-10]-carrier wherein the peptide 1-N.sup.α-glutaryl-LH-RH-[2-10] is linked to poly-L-lysine carrier by a peptide linkage between the carboxyl group of the glutaryl moiety and the ε-amino groups of lysyl residues in poly-L-lysine.
Claim 4
Dependent Claim
33 words
The antigen 1-N.sup.α-glutaryl-LH-RH-[2-10]-carrier wherein the peptide 1-N.sup.α-glutaryl-LH-RH-[2-10] is linked to poly-L-lysine carrier by a peptide linkage between the carboxyl group of the glutaryl moiety and the ε-amino groups of lysyl residues in poly-L-lysine.
Claim 5
Dependent Claim
20 words
The antigen according to claim 2 wherein the average molecular weight of the poly-L-lysine carrier is between 40,000 and 80,000.
Claim 6
Dependent Claim
8 words
The peptide having the structure: glutaryl-his-trp-ser-tyr-gly-leu-arg-pro-gly-NH 2 .
Claim 7
Dependent Claim
8 words
The peptide having the structure: glutaryl-his-trp-ser-tyr-gly-leu-arg-pro-gly-NH 2 .
Claim 8
Dependent Claim
179 words
The process for preparing the antigen 1-N.sup.α-glutaryl-LH-RH-[2-10]-carrier which comprises: a. reacting the methyl or ethyl ester of histidine with glutaric anhydride to form the dipeptide N.sup.α-glutaryl-his-OMe or N.sup.α-glutaryl-his-OEt; b. reacting said dipeptide, N.sup.α-glutaryl-his-OMe or N.sup.α-glutaryl-his-OEt, with hydrazine to form the corresponding hydrazide, N.sup.α-glutaryl-his-NHNH 2 ; c. reacting said hydrazide, N.sup.α-glutaryl-his-NHNH 2 , with isoamyl nitrite to form the azide, N.sup.α-glutaryl-his-N 3 ; d. reacting said azide, N.sup.α-glutaryl-his-N 3 , with the methyl or ethyl ester of trp-ser-tyr to form the corresponding pentapeptide N.sup.α-glutaryl-his-trp-ser-tyr-OMe or N.sup.α-glutaryl-his-trp-ser-tyr-OEt; e. reacting said pentapeptide, N.sup.α-glutaryl-his-trp-ser-tyr-OMe or N.sup.α-glutaryl-his-trp-ser-tyr-OEt, with hydrazine and isoamyl nitrite as in step b) and c) to form the azide, N.sup.α-glutaryl-his-trp-ser-tyr-N 3 ; f. reacting said azide, N.sup.α-glutaryl-his-trp-ser-tyr-N 3 , with the pentapeptide, gly-leu-arg-pro-gly-NH 2 , thereby forming the decapeptide having the amino acid sequence, glutaryl-his-trp-ser-tyr-gly-leu-arg-pro-gly-NH 2 and linking said decapeptide by a peptide linkage between the carboxyl group of the glutaryl moiety of the decapeptide and the amino groups of a carrier selected from the group consisting of α, β and γ globulins, thyroglobulins, Keyhole Limpet Hemocyanin, poly-L-glutamic acid and poly-L-lysine.
Claim 9
Dependent Claim
179 words
The process for preparing the antigen 1-N.sup.α-glutaryl-LH-RH-[2-10]-carrier which comprises: a. reacting the methyl or ethyl ester of histidine with glutaric anhydride to form the dipeptide N.sup.α-glutaryl-his-OMe or N.sup.α-glutaryl-his-OEt; b. reacting said dipeptide, N.sup.α-glutaryl-his-OMe or N.sup.α-glutaryl-his-OEt, with hydrazine to form the corresponding hydrazide, N.sup.α-glutaryl-his-NHNH 2 ; c. reacting said hydrazide, N.sup.α-glutaryl-his-NHNH 2 , with isoamyl nitrite to form the azide, N.sup.α-glutaryl-his-N 3 ; d. reacting said azide, N.sup.α-glutaryl-his-N 3 , with the methyl or ethyl ester of trp-ser-tyr to form the corresponding pentapeptide N.sup.α-glutaryl-his-trp-ser-tyr-OMe or N.sup.α-glutaryl-his-trp-ser-tyr-OEt; e. reacting said pentapeptide, N.sup.α-glutaryl-his-trp-ser-tyr-OMe or N.sup.α-glutaryl-his-trp-ser-tyr-OEt, with hydrazine and isoamyl nitrite as in step b) and c) to form the azide, N.sup.α-glutaryl-his-trp-ser-tyr-N 3 ; f. reacting said azide, N.sup.α-glutaryl-his-trp-ser-tyr-N 3 , with the pentapeptide, gly-leu-arg-pro-gly-NH 2 , thereby forming the decapeptide having the amino acid sequence, glutaryl-his-trp-ser-tyr-gly-leu-arg-pro-gly-NH 2 and linking said decapeptide by a peptide linkage between the carboxyl group of the glutaryl moiety of the decapeptide and the amino groups of a carrier selected from the group consisting of α, β and γ globulins, thyroglobulins, Keyhole Limpet Hemocyanin, poly-L-glutamic acid and poly-L-lysine.
Claim 10
Dependent Claim
54 words
The process according to claim 5 for preparing the antigen, 1-N.sup.α-glutaryl-LH-RH-[2-10]-poly-L-lysine, which comprises steps (a) to (f) to form the decapeptide having the amino acid sequence, glutaryl-his-trp-ser-tyr-gly-leu-arg-pro-gly-NH 2 , and linking said decapeptide by a peptide linkage between the carboxyl group of the glutaryl moiety and the ε-amino groups of lysyl residues in poly-L-lysine.
Claim 11
Dependent Claim
40 words
The process according to claim 6 wherein the process comprises forming the active ester of the peptide having the amino acid sequence glutaryl-his-trp-ser-tyr-gly-leu-arg-pro-gly-NH 2 with [1-hydroxybenzotriazole] and reacting said active ester with the ε-amino groups of lysyl residues in poly-L-lysine.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1979-06-15 | 1979-12-15 | 1980-06-15 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1983-06-15 | 1983-12-15 | 1984-06-15 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1987-06-15 | 1987-12-15 | 1988-06-15 | $7700.00 | Window Closed / Lapsed |