The Biopharmaceuticals An Overview Biology Essay

The Biopharmaceuticals An Overview Biology EssayBiopharmaceuticals be defined as proteins and nucleic blisterys which be utilisationd for therapeutic purpose. These ar high molecular weight substances inclined(p) by bio scientific means and familialally engineered. Due to their complex social system and abstruse molecular composition it is actually difficult to characterize and formulate much(prenominal)(prenominal) products. Most of these products be derived from biological species and genetically engineered to nurture a starchy compound 1-3. Humulin (biosynthetic recombinant tender-hearted Insulin) was the graduation biopharmaceutical product coached by Genentech but licensed and merchandiseed by Eli Lily and Company in 1982. In the raw era biopharmaceutical products withdraw become a major facilitating reason of technological changes in wellness c atomic number 18 vault of heaven, create extraordinary benefits for patients, cost challenges for consumers, an d net for foodstuffplace sh beholders.4Over the last decade biopharmaceutical market is the fastest developing segment in the pharmaceutical organizations. After post-recession period vigorous furtherance has been seen in this bowl of operations. It has been reported that approximately 40% of total pharmaceutical RD investiture is occupied by biopharmaceutical products amongst which, monoclonal antibodies and product produced by recombinant DNA regularity be the most prevalent whizz.5,6 Proteins with different amino acid sequences ar the primary structure of such(prenominal)(prenominal) products. For determining the biological activity of a protein it is necessary to study its three-dimensional structure. The structure of protein is generally divided into quaternity categories i.e. primary, secondary, tertiary and quaternary (fig. 1). The primary structure is the sequence of amino acid residues which folds and stabilized by the formation of hydrogen bonds with subsequ ent elements in the polypeptide twine to produce an helix,which is a spiral, rod- desire structure, or a sheet,a planar structure. This structure resembles to the secondary structure of proteins. The tertiary structure is a three-dimensional organisation which gives an overall conformation of a polypeptide chain. Through hydrophobic interactions between the non-polar cheek chains and disulfide bonds, this tertiary structure is stabilized. A quaternary or multimeric protein contains deuce or to a greater extent polypeptide chains, held together by non-covalent bonds.7fig 1. Structure of protein.Because of their uncommon physico chemic substance characteristic it is in truth hard and challenging to formulate biopharmaceuticals as products with therapeutic effects and storage characteristics. slowdown their formulation is in many a(prenominal) ways different from conventional low-molecular dose formulation. Despite of such facts biopharmaceuticals gains haemorrhoid of attentio n in the modern era of dose formulation. In the young reviews it has been discussed that around four hundred biotechnology-based healthful and therapeutic agents are either registered or in the clinical trials are reviewed by the regulative bodies. These agents are subservient in treating many life threatening diseases about of them are cancer, morbific diseases, autoimmune diseases, and AIDS/HIV. Some of the agents which are already in the market are monoclonal antibodies, recombinant hormones, cytokines, vaccines, recombinant blood factor, and therapeutic enzymes.5DiscussionBiopharmaceutical marketIn 1970, discovery of recombinant DNA technology and monoclonal antibodies lead to initiate the maturement of biopharmaceutical industries. A substantial growth from $8 one million million million in 1992 to $149 billion in 2010 quenched the thirst of investors towards the biopharmaceutical industry. It is expected to reach $239 billion by 2015 with a growth rank of 9.9% annual ly. in that respect are more than 400 Biotech drugs and vaccines are scrutinized on a lower floor clinical stage, targeting more than 200 diseases. Meanwhile a boastful figure of the population is now taking benefits from a number of biotechnological innovations like recombinant protein-based products e.g. monoclonal antibodies and near large molecule prescription drugs, which embarrass hormones and vaccines. Table 1 illustrates around of the leading biopharmaceutical therapy course of instructiones by size ecumenical in 2002. In 2008 approximately 39%, among the cap 10 drugs merchandise orbiculately, are biopharmaceuticals and is expected to rise to 79% of the top 10 drug sales by 2014.8Table.1 Leading biopharmaceutical therapy classes by size worldwide 2002. initiation IMS MIDAS December 2002. hitherto after the post recession period, fundings over health care and other sector is reduced which impede the growth rate of pharmaceutical industries up to prodigious exten t. Although biopharmaceutical global sales thrive to come to high numbers in the global health sector. Biotechnological based products bring forth generated $229 billion revenue in 2012 with an annual growth rate of 10.4%. Meanwhile the major focus of pharmaceutical organizations is on biopharmaceutical vs. Small molecule drugs which enables to allot high funding towards this area. This may be due to very less(prenominal) generic biosimilar products available in the market. In year 2009 in that respect are total 18 biopharmaceutical products are approved by US FDA which is high than the previous years i.e. 11 in 2008 and 10 in 2007. In a report of Battelle Technology Partnership Practice, it was estimated that the overall touch on of biopharmaceutical sector on the US economy is $917 billion. These companies are making alliances with other inhering services such as computing and information, clinical trial and regulatory support services, technologies, manufacturing and equip ment, and transportation and logistics providers.9-11Types of BiopharmaceuticalsCytokinesCytokines are a diverse group of non-antibody inter carrellular guideling regulatory proteins i.e. glycoprotein and low molecular weight peptides produced in very puny amount inside the body. They function as a mediator for conference between various mobile phones and induce certain response by medical dressing to specific cell surface receptors which results in triggering various intracellular signal transduction mechanism. there are over 80 sub class of cytokines have been found. Some of these are categorized in table 2. They play an master(prenominal) role in coordinating embryonic development, cell growth and maturation, irritate repair and healing, the immune response including acute phase reactions and septic shock, and newly blood vessel formation. Cancer is among the major class of disease which is well scrutinized by the researchers with an emphasis on cytokines. However cytok ines also play a vital role in mediating signalling response to systemic inflammation which tends to set up specific neuronal network to induce sickness. Some animal studies light upon the role of cytokines in situations characterized by abnormal snooze, with emphasis on the pathogenesis of symptoms and consequences of OSAS (Obstructive sleep apnoea syndrome). Cytokines interact with specific cells via (1) intracrine, in which both cytokine and receptor remain indoors the cell (rare) (2) autocrine, where a cytokine acts on the receptors of the same cell it is produced and (3) paracrine, where the cytokine from one cell type interacts with receptors on other cell types.12-16Table 2 sorting of cytokines.There are various cytokines products available in the market and some of them are reviewed under the clinical phase for example Interleukin-2 (IL-2) aldesleukin (Proleukin), for treating renal cell carcinoma is approved by FDA. IL-1 blocker, anakinra (Kineret) and rilonacept (Arca lyst) are employ for the interposition of rheumatoid arthritis and cryopyrin-associated half-yearly syndromes respectively.1EnzymesEnzymes are complex molecules produced by musical accompaniment cells. They increase the rate of chemical reaction without even showing their own effect in the influence and hence act as a catalyst in living organisms.17 Because of their reaction specificity, catalytic efficiency and susceptibility to operate under kooky condition of temperature and hydrogen ion concentration they are preferred as a novel class of therapeutic agents. Despite of their therapeutic role enzyme endures prodigious importance as a replacement therapy in many genetic disorders. However there are some disadvantages as well associated with their use such as, their parental administration required extensive purification to back out contaminants. They are also very costly to prepare and due to their large molecular structure they have limited scattering in the body. As th ey are proteins hence when administered inside the body act as antigen to the boniface cell.18,19Enzymes are categorized under six major classes i.e transferases, lysases, hydrolases, isomerases, ligases, and oxidoreductases. The capability expediency of enzyme as pharmaceutical was noted many decades ago. However most of the enzyme therapies are used to treat functional defects. Activase (alteplase recombinant adult male tissue plasminogen activator), is the first recombinant enzyme drug which was approved by the Food and Drug Administration in 1987. Pulmozyme (Dornase alpha), a recombinant DNAse I that digests DNA in the mucous secretions in lungs, used to treat cystic fibrosis. Adagen (pegadamase bovine), is the first marketed product as enzyme therapy for the treatment of severe combined immunodeficiency (severe combined immunodeficiency disease).20HormonesHormone is characterized as an significant group of regulatory molecule which is synthesized in an organ or in tissue and then secreted into circulative system where it affects respective organs whose cell bears an appropriate receptors. They are chemical messengers either small or a large macromolecule and are fairly defined as internal secretion hormones. Approximately all endocrine hormones possess therapeutic importance and hence subsequently used by the researchers e.g. insulin(Insugen, Humulin, Novolin), human growth hormone (Ascellacrin, Crescormon), glucagon, and the gonadotrophins.1AntibodiesAntibodies or immunoglobulin are proteins produced, as an immune response, through white blood cells when a unusual particle or antigen intrudes inside the body. There are five classes of immunoglobulin IgE, IgM, IgG, IgD, and IgA. Amongst them IgG is the most common as a biopharmaceutical agents. A more specified term i.e. monoclonal antibodies (mAbormoAb) are the novel class compounds that are first developed in mid 1970s by kohler and Milstein, who successfully fused immortal cells with antibody- producing B lymphocytes. This fusion results in a hybrid which is stable, cancerous, antibody- producing cells. These are referred as hybridoma cells which unveil great source of monoclonal antibody. mAb identify antigens on a particular foreign body very specifically. mAbs are categorized under four groups according to their source murine (derived solely from mice), chimeric (mixture of murine and human sequences), humanised (contain over 90% human sequences) and fully human.8,17 In 1986, Murobmonab (OKT3), a murine antibody, is the first monoclonal antibody well-tried as a therapeutic in humans. However it fails to produce a substantial response in the transplantation rejection patients because of production of anti-murine antibody.20Monoclonal antibodies are the fastest growing therapeutic class in the field of biopharmaceutical market. The market of monoclonal antibodies crosses the mark of $30 billion in 2011. Infliximab (Remicade) is the top merchandising monoclonal antibody in 2002 which was developed by Centocor and is marketed by Centocor and Schering-Plough for the treatment of rheumatoid arthritis (RA) and Crohns disease. Rituximab (Rituxan), developed by Genentech and IDEC and marketed by Genentech, IDEC and Roche, for the treatment of non-Hodgkins lymphoma, is the second largest selling monoclonal antibody.21VaccinesVaccines are antigenic proteins which are either partial or modified form of bacteria, viruses and toxins which causes certain diseases against which vaccine protects. The antigenic property of vaccines is adapted from its original form by certain processes such as utilizing thinned viruses, inactivated viruses, part of a virus or bacteria and toxin produced by bacteria hence they lack ability to cause disease although, endures ability to produce an immune response.22 Vaccines are the only known prophylactic approach which are commonly available to cure many infective diseases. Vaccines cover the global market share of $ 3 billion a nnually. Government health agencies exploit different immunization programs which alleviate the risk of many infective disorders. However, there are approximately 15 million people die any year from certain morbific diseases that can be cured by vaccination process. Pharmaceutical and biopharmaceutical industries seek great potential in this area but the use is limited because of their high production cost, delivery and distribution problems. Vaccines may contain animal derived products such as Bovine blood serum albumin or fetal calf serum or human derived product for example employ cell lines of human tissues. However in recent years transgenic and recombinant plants are also utilized for the production of vaccines.12,23,24 There are different vaccines available in the market for many infectious diseases such as poliomyelitis, cholera, diphtheria, tetanus, hepatitis B, hepatitis A, measles, meningitis etc. For hepatitis B virus some examples are Baraclude (Entecavir), Adefovi r dipivoxil (Hepsera), Lamivudine (Epivir-HBV, 3TC), Alfa Interferon (Intron A, Infergen, Roferon).1,25Antisense drugsAntisense compounds are non-coding strand of messenger ribonucleic acid(mRNA), which hybridize with mRNA and inactivates the ability of genes to produce the protein for which it holds the recipe.26 They do not alter human gene causing variation in human genetic information. It was first developed in 1978 using a string of DNA nucleotide which binds with messenger RNA and block its function. These drugs are designed to treat a wide bunk of diseases such inflammatory, infectious, cancer and cardiovascular diseases. Fomiversen was the first antisense drug approved in 1998 for the treatment of cytomegalovirus retinits in AIDS patients. These are categorized under three sub-classes i.e. antisense oligonucleotides(ASONs), ribozymes and RNA interference(RNAi). Affinitak, fabricate by ISIS pharmaceuticals and Eli Lilly, is used for the treatment of non-small-cell lung carc inoma(NSCLC). There are certain antisense compound are under review by health agencies for their therapeutic efficacy towards many anomalies27,28Peptide therapeuticsPeptides are polymers having one or two amino acids linked with amides and are chemically synthesized by using liquid phase or solid phase entailment. Their chemical synthesis is preferred over biosynthetic approach because it facilitates the conjugation or internalization of small molecules and non-natural amino acids. This approach reveals the potential of such molecules as cytotoxic agents for antitumor therapy. Peptides with non-natural opens up the possibility for greater chemical diversity, analogous to small-molecule medicinal chemistry approaches for developing high-afnity, highspecicity molecular designation. Cationic antimicrobial peptides (CAMPs) and peptidoglycan recognition proteins (PGRPs)are developed from the effectors of innate immune response in eukaryotes during their defense mechanism. However there are not many products of peptides found in the market but researchers are trying to develop some therapeutic peptides and proteins with significant effect towards certain diseases. Nesiritide (Natrecor, Noratak) is produced by Johnson Johnson2001, Teriparatide (Forteo) is developed and marketed by Lily in 2002 Enfuvirtide (Fuzeon) is manufactured by Trimeris 2003.29-31Challenges associated with biopharmaceutical productsBiopharmaceutical products such as monoclonal antibodies, vaccines, certain hormones, and cell therapies are rewarded as some of the most promising innovation in the field of medicine and health. However there are certain risk and challenges associated with such products which hamper their performance. One of the major challenges is the purification of proteins although it can be achieved by various processes but still purification of such compound is very critical hence requires a lot of attention during manufacturing. Next contemporaries pharmaceutical.32However the whole process is carried out under two phases i.e. upriver and downstream regulation. Immunogenicity associated with some of these proteins is also a major concern for biopharmaceutical agents. A repeated injection of human protein may affect the immune gross profit margin towards self- antigen, leading to humoral response.33Biopharmaceutical products require greater attention, process level as well as monitory level, in the development phase of the drug discovery process it requires approximately $200 million to develop a biopharmaceutical product hence the risk associated with their failure during development stage is increased. by from purification and immunogenicity some other issues also make some impact during their development such as government regulations which influence the cost of such products. As discussed earlier it takes a large amount of money to develop such agents hence companies also compensate their development cost and elucidate profits from their produ cts, ones marketed, which exponentially increases the cost of the drugs.Last and one of the most important risk associated with such products is the introduction of biosimilar products. Biopharmaceutical market is growing very fast, the initial compounds of the first generation are now coming to an end. The expiry of the patents opens the market for generic products which not only influence the established market of some very popular brands, it also forms a milieu of competition to sell the products at cheaper rates which is compensated by their quality.34ConclusionBiopharmaceutical products are one amongst the novel class of therapeutic compounds. These are medical agents obtained from biological sources and some special one are manufactured by biotechnological means. They are cellular products, therapeutic proteins, vaccines, gene therapy products and plasma blood product derivatives. Erythropoietins, insulins, and monoclonal antibodies, are some of the leading biopharmaceutical p roducts available in the market hence biopharmaceutical companies are now focusing on their use in long-term conditions such as cardiovascular disease, diabetes and asthma. The blockbuster sales of some existing biopharmaceutical products attach to by the tremendous innovation and a plethora of pipeline products examine the vigorous growth in the biopharmaceutical market in upcoming years. This significant growth is supported by some of the key segments of the field like monoclonal antibody and vaccines. In addition approaches like gene therapy and peptide therapeutics holds enormous potential for some life threatening anomalies and the combined approach of proteomics, genomics and biotechnology is predicted to invest the most part of the healthcare sector in the upcoming days.