➤ Get the DrugPatentWatch Daily Briefing

Get Daily Updates on Generic Entry, Litigation, Biosimilars, and more …

Serving leading biopharmaceutical companies globally:

McKesson
Moodys
Boehringer Ingelheim
Mallinckrodt
Express Scripts
Merck

Last Updated: September 18, 2021

DrugPatentWatch Database Preview

Claims for Patent: 4,427,827

➤ Get the DrugPatentWatch Daily Briefing

« Back to Dashboard

Summary for Patent: 4,427,827
Title: Synthesis of hormone fragments
Abstract:The yield of peptide synthesis processes of the type in which a protected intermediate resin peptide of the formula Resin--CH.sub.2 --O--Phe--X, Resin--CH.sub.2 --O--Gly--X, Resin--CH.sub.2 --O--Ala--X, or Resin--CH.sub.2 --O--Leu--X is deprotected, and successively protected amino acids are coupled to the resin peptide and deprotected, is increased significantly by deprotecting the first residue with trifluoroacetic acid and deprotecting the other residues with hydrogen chloride.
Inventor(s): Stevenson; David (Scarsdale, NY)
Assignee: USV Pharmaceutical Corporation (Tarrytown, NY)
Application Number:06/435,581
Patent Claims:1. In the synthesis of a resin peptide of the formula R--CH.sub.2 --O--Z, from an intermediate resin peptide of the formula R--CH.sub.2 --O--Y--X wherein

R is an insoluble polystyrene resin;

Y is a terminal amino acid residue selected from the group consisting of Phe, Gly, Leu and Ala;

X is a protecting group in the .alpha.-amino position of Y; and

Z is either

a fragment (n-m) of human parathyroid hormone or an analog thereof in which Y is Phe and m is 34; Y is Gly and m is 12; or Y is Leu and m is 7, 11, 15, 24, or 28; and n is an integer from 1 to (m minus 1); or

a fragment (n-m) of human calcitonin or an analog thereof in which Y is Phe and m is 5, 6, or 11; Y is Gly and m is 2, 10, 28, or 30; Y is Leu and m is 4 or 9; or Y is Ala and m is 26 or 31; and n is an integer from 1 to (m minus 1);

wherein the residue Y is deprotected and neutralized and in succession each of the other amino acids whose residues comprise the fragment Z, each having a protecting group in the .alpha.-amino position, is coupled to the next preceding residue on the resin peptide and then deprotected and neutralized, the improvement comprising

(a) deprotecting the residue Y with trifluoroacetic acid, and

(b) deprotecting the other residues with hydrogen chloride dissolved in a solvent selected from the group consisting of dioxane and ethers containing from 4 to 6 carbon atoms.

2. In the synthesis of a resin peptide of the formula R--CH.sub.2 --O--Z, from an intermediate resin peptide of the formula R--CH.sub.2 --O--Y--X wherein

R is an insoluble polystyrene resin;

Y is a terminal amino acid residue selected from the group consisting of Phe, Gly, and Leu;

X is a protecting group in the .alpha.-amino position of Y; and

Z is a fragment (n-m) of human parathyroid hormone or an analog thereof in which Y is Phe and m is 34; Y is Gly and m is 12; or Y is Leu and m is 7, 11, 15, 24, or 28; and n is an integer from 1 to (m minus 1);

wherein the residue Y is deprotected and neutralized and in succession each of the other amino acids whose residues comprise the fragment Z, each having a protecting group in the .alpha.-amino position, is coupled to the next preceding residue on the resin peptide and then deprotected and neutralized, the improvement comprising

(a) deprotecting the residue Y with trifluoroacetic acid, and

(b) deprotecting the other residues with hydrogen chloride dissolved in a solvent selected from the group consisting of dioxane and ethers containing from 4 to 6 carbon atoms.

3. The process of claim 1 wherein the hydrogen chloride has a concentration of about 3.5 N to about 4.0 N and the solvent is dioxane.

4. The process of claim 3 wherein the hydrogen chloride solution also contains about 1 vol. % to about 2 vol. % of a thiol.

5. The process of claim 4 wherein the thiol is 2-mercaptoethanol.

6. The process of claim 1 wherein the protecting group removed in each deprotecting step is t-butyloxycarbonyl.

7. The process of claim 1 wherein the trifluoroacetic acid is dissolved in toluene, methylene chloride, or a mixture thereof.

8. The process of claim 1 wherein n is 1.

9. The process of claim 1 wherein Z is a fragment (28-34) of human parathyroid hormone, and Y is Phe.

10. The process of claim 1 wherein Z is a fragment (5-12) of human parathyroid hormone, and Y is Gly.

11. The process of claim 1 wherein Z is a human parathyroid hormone fragment, Y is Leu, m is 7, 11, 15, 24, or 28, and n is (m minus 6).

12. The process of claim 9 wherein the hydrogen chloride has a concentration of about 3.5 N to about 4.0 N and the solvent is dioxane.

13. The process of claim 10 wherein the hydrogen chloride has a concentration of about 3.5 N to about 4.0 N and the solvent is dioxane.

14. The process of claim 11 wherein the hydrogen chloride has a concentration of about 3.5 N to about 4.0 N and the solvent is dioxane.

Details for Patent 4,427,827

Applicant Tradename Biologic Ingredient Dosage Form BLA Number Approval Date Patent No. Assignee Estimated Patent Expiration Status Orphan Source
Nps Pharms Inc NATPARA parathyroid hormone INJECTABLE;INJECTION 125511 001 2015-01-23 ⤷  Free Forever Trial USV Pharmaceutical Corporation (Tarrytown, NY) 2039-03-29 RX Orphan search
Nps Pharms Inc NATPARA parathyroid hormone INJECTABLE;INJECTION 125511 002 2015-01-23 ⤷  Free Forever Trial USV Pharmaceutical Corporation (Tarrytown, NY) 2039-03-29 RX Orphan search
Nps Pharms Inc NATPARA parathyroid hormone INJECTABLE;INJECTION 125511 003 2015-01-23 ⤷  Free Forever Trial USV Pharmaceutical Corporation (Tarrytown, NY) 2039-03-29 RX Orphan search
>Applicant >Tradename >Biologic Ingredient >Dosage Form >BLA >Number >Approval Date >Patent No. >Assignee >Estimated Patent Expiration >Status >Orphan >Source

Make Better Decisions: Try a trial or see plans & pricing

Serving leading biopharmaceutical companies globally:

Merck
Mallinckrodt
Medtronic
Harvard Business School
McKinsey
Boehringer Ingelheim

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.