Research Exemption Peptides

Over the past two decades, there have been many peptide drugs approved for treating a variety of diseases. Once the product has achieved regulatory approval by having completed and passed clinical trials determining it to be safe and effective, it becomes a marketed Brand drug. Manufacturers of generic peptide drugs are able to utilize the original manufacturer’s approval provided that they can show that the generic peptide drug is bio-equivalent to the approved Brand drug. The generic producer is able to run their clinical trials, tests and studies on their generic peptide without infringing upon the original manufacturer’s patented drug before the patent has expired by way of the Bolar exemption in Europe and the UK (including Canada) and Merck vs. Integra for the USA.

Some of the most important of these peptide drugs are available from Peptides International and include:

Semaglutide, GLU-3875-PI: is a glucagon-like peptide-1 (GLP-1) analogue and a GLP-1 receptor agonist. Not only does it have a half-life of up to one week, it has been used in type 2 diabetes research for its ability to stimulate insulin production while suppressing glucagon secretion in a glucose-dependent manner. Semaglutide has an increased albumin affinity and exhibits a three-fold decrease in GLP-1 receptor affinity when compared to liraglutide.1 Recent studies in patients with type 2 diabetes suggest that semaglutide may also have an improved cardiovascular outcome in those patients who are at risk for a cardiac event.2            

  1. J. Lau, et al., J. Med. Chem., 58, 7370 (2015). Retrieved from http://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.5b00726
  2. S.P. Marso, et al., N. Engl. J. Med., 375, 1834 (2016). Retrieved from http://www.nejm.org/doi/full/10.1056/NEJMoa1607141#t=article

Pramlintide, PAM-3824-PI: Pramlintide is an analogue of amylin, a small peptide hormone that is released into the bloodstream by the β-cells of the pancreas along with insulin after a meal.1  Like insulin, amylin is completely absent in individuals with Type I diabetes.2  By augmenting endogenous amylin, pramlintide aids in the cellular absorption and regulation of blood glucose by slowing gastric emptying, promoting satiety via hypothalamic receptors (different receptors than for GLP-1), and inhibiting inappropriate secretion of glucagon, a catabolic hormone that opposes the effects of insulin and amylin. Pramlintide also has effects in raising the acute first-phase insulin response threshold following a meal. Both a reduction in glycated hemoglobin and weight loss have been shown in insulin-treated patients with type 2 diabetes taking pramlintide as an adjunctive therapy.3

  1. M.C. Jones, "Therapies for diabetes: pramlintide and exenatide" (pdf). American Family Physician, 75 (12), 1831 (2007). PMID 17619527.
  2. S. Edelman, et al., "Pramlintide in the Treatment of Diabetes Mellitus". BioDrugs, 22 (6), 375 (2008). doi:10.2165/0063030-200822060-00004.ISSN 1173-8804.
  3. P. Hollander, et al., "Effect of Pramlintide on Weight in Overweight and Obese Insulin-Treated Type 2 Diabetes Patients" (pdf). Obesity, 12(4), 661 (2004). doi:10.1038/oby.2004.76. ISSN 1930-7381.

Octreotide, PCI-3738-PI: This disulfide-rich peptide is used for the treatment of growth hormone producing tumors, pituitary tumors that secrete thyroid
stimulating hormone, and diarrhea in patients with VIP-secreting tumors.

Enfuvirtide, ENF-3787-PI: This 36 residue peptide blocks the entry of the HIV virus by binding to the virus gp41 protein. This prevents a conformational change in gp41 which is necessary for the virus to fuse and form the entry pore for the capsid of the virus into the CD4+ T-cell, and keeps it from entering the cell. This peptide drug has been used success fully in HIV patients as part of a combination therapy with protease and reverse transcriptase inhibitors.

Eptifibatide, EPT-3786-PI: Originally derived from a protein obtained from the venom of Southeastern Pygmy Rattlesnake, this cyclic heptapeptide is an anti-platelet drug which binds to the glycoprotein IIb-IIIa. The drug has a very short half life and is used to reduce the risk of acute cardiac ischemic events in patients with unstable angina or in patients with non-ST-segment elevation myocardial infarction.

Exenatide - Exendin-4, PEX-3784-PI: This 39 residue peptide was originally isolated from the saliva of the Gila Monster. The peptide is a GLP-1 (glucagon like peptide) agonist and is an insulin secretagogue with glucoregulatory effects. It has been used extensively in treating type II diabetes in combination with metformin and pioglitazone.

Linaclotide, LIN-3796-PI: This disulfide-rich peptide is an agonist of gaunylate cyclase 2c. It is currently approved as an orally delivered treatment for chronic constipation.

Liraglutide, PGL-3781-PI: This peptide is a long acting GLP-1 agonist and is an acylated variant of human GLP-1 (7-37). The selective fatty acylation of the peptide increases the half life to 11-15 hours following a subcutaneous injection allowing for once daily injection. This peptide drug has been widely used to treat type II diabetes.

Tetracosactide - ACTH (Human,1-24) PAC-4109-v: This pep- tide drug is derived from the N-terminal 24 amino acids from the naturally occurring peptide hormone ACTH (adrenocorticotropin hormone). This peptide hormone induces an increase in the levels of circulating glucocorticoids and is primarily used as a diagnostic for proper function of the adrenal glands. It has also been classified as a doping agent or performance enhancing drug (PED) in cycling.

Teriparatide - Parathyroid Hormone (Human, 1-34) PTH- 4068-s: This 34 residue parathyroid hormone (PTH 1-34) has been used to treat osteoporosis. This peptide is derived from PTH-1-84. PTH 1-34 is the primary regulator of calcium and phosphate metabolism in bone and kidney. PTH increases calcium levels by stimulating bone resorption. When used intermittently, the effect stimulates osteoblasts more than osteoclasts, thereby resulting in new bone formation.

Nesiritide - BNP-32 (Human), PBN-4212-v: This drug is a 32 residue B-type natriuretic peptide. This peptide is normally produced by the ventricular myocardium. Nesiritide works to facilitate cardiovascular fluid homeostasis through coun- ter-regulation of the renin-angiotensin-aldoesterone system, stimulating cyclic guanosine monophosphate, leading to smooth muscle cell relaxation.

Bivalirudin, BIV-3767-PI: This peptide drug is a direct and reversible thrombin inhibitor. Originally derived from hiruidin, the salivary anticlot protein found in leeches, this 20 residue peptide congener inhibits both circulating and clot bound thrombin as well as inhibiting platelet activation and aggregation in a highly specific and reversible manner. Bivalirudin clinical studies demonstrated consistent positive outcomes in patients with stable angina, unstable angina (UA), non-ST segment elevation myocardial infarction (NSTEMI).

Ziconotide - ω-Conotoxin MVII-A, PCN-4289-v: This 25 residue 3 disulfide peptide is a non-opioid, non-NSAID drug used to treat patients with chronic intractable pain. Originally derived from the cone snail, Conus magus, this peptide is a potent blocker of N-type Ca+2 channels.

Lixisenatide - Lyxumia, LIX-3799-PI: This peptide is a GLP-1 receptor agonist. Originally discovered by Zealand Pharma, it was licensed and developed by Sanofi for its use in the treatment of Type 2 diabetes. GLP-1 is a natually occuring peptide, released shortly after a meal has been consumed.

Teduglutide, TED-3880-PI: This is a 33 amino acid, glucagon-like peptide-2 (GLP-2) analog, used for the treatment of short bowel syndrome. It does this by promoting mucosal growth and possibly restoring gastric emptying and secretion. It differs from the natural GLP-2 by an alanine that has been replaced with a glycine.

 

Authors from Peptides International

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