4^th Antibodies, Antibiotics and Bio Therapeutics Congress: R&D, Market and B2B

The evidence indicates that two simian immunodeficiency viruses (SIV), one from Chimpanzees (SIVcpz) and the other from sooty mangabeys (SIVsm), crossed the species barrier to humans, generating HIV-1 and HIV-2, respectively. The importance of characterizing the prevalence, geographic distribution, and genetic diversity of naturally occurring SIV infections to investigate whether humans continue to be exposed to SIV and if such exposure could lead to additional zoonotic transmissions. Through vigorous efforts made in the past two centuries, public health workers have succeeded in developing vaccines, antibiotics, and chemotherapeutics, and as a result most infectious diseases have been brought under control in industrialized countries. However, in developing countries, infectious diseases have been harder to contain, and the increase in migration and movement of populations in the last two decades has made national boundaries disappear as far as the transmission of infection is concerned. Some diseases, such as malaria, have been eradicated from industrialized countries mainly through extensive work on vector control, but their presence in developing countries has increased because of neglect or drug resistance. One of these proteases (Histidine Aspartic Protease, HAP) is homologous to three other aspartic proteases involved in hemoglobin metabolism but has a histidine in place of one of the two aspartic acids involved in catalysis.

Auto-antibody is an antibody formed in response to, and reacting against, an antigenic constituent of the individual's own tissues. Several mechanisms may trigger the production of autoantibodies: an antigen, formed during fetal development and then sequestered, may be released as a result of infection, chemical exposure or trauma, as occurs in autoimmune thyroiditis, sympathetic uveitis and aspermia; there may be disorders of immune regulatory or surveillance function.     

Monoclonal antibody therapy is a process in which monoclonal antibodies (mAb) are used to bind monospecifically to certain cells or proteins. This may then stimulate the patient's immune system to attack those cells. Alternatively, in radioimmunotherapy a radioactive dose localizes on a target cell line, delivering lethal chemical doses. More recently antibodies have been used to bind to molecules involved in T-cell regulation to remove inhibitory pathways that block T-cell responses, known as immune checkpoint therapy. It is possible to create a mAb specific to almost any extracellular/ cell surface target. Research and development is underway to create antibodies for diseases (such as rheumatoid arthritis, multiple sclerosis, Alzheimer's disease, Ebola and different types of cancers).    

Antibodies are used extensively as diagnostic tools in many different formats. The term applied for antibody based diagnostic tests is “immunoassay”. Antibody-based immunoassays are the most commonly used confirmatory diagnostic assays and is the fastest growing technologies for the analysis of biomolecules. Trends in antibody based diagnosis show advances in assay specificity, detection technologies and sensitivity. Sensitivity and specificity is ensured depending on whether or not the antigen to be quantified competes with labeled antigen for a limited number of antibody binding sites. Monoclonal antibodies are now widely used in all areas of biological and medical research as well as in clinical diagnostic tests and in therapy. This review concentrates on the clinical use of antibodies in therapy particularly with regard to the properties of the antibodies which seem most relevant to their usefulness. In-vitro tests using human effector systems and in-vivo animal models have demonstrated the importance of the antibody isotype and valency for antigen as well as the specificity of binding.

Antibody therapies are the most successful immunotherapy, treating a wide range of cancers. Antibodies are proteins produced by the immune system that bind to a target antigen on the cell surface. In normal physiology the immune system uses them to fight pathogens. Each antibody is specific to one or a few proteins. Those that bind to cancer antigens are used to treat cancer. Cell surface receptors are common targets for antibody therapies. Among the most promising approaches to activating therapeutic antitumor immunity is the blockade of immune checkpoints. Immune checkpoints refer to a plethora of inhibitory pathways hardwired into the immune system that are crucial for maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses in peripheral tissues in order to minimize collateral tissue damage. It is now clear that tumors co-opt certain immune-checkpoint pathways as a major mechanism of immune resistance, particularly against T cells that are specific for tumor antigens. Because many of the immune checkpoints are initiated by ligand–receptor interactions, they can be readily blocked by antibodies or modulated by recombinant forms of ligands or receptors. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) antibodies were the first of this class of immunetherapeutics to achieve US Food and Drug Administration (FDA) approval.

Conventional anticancer therapeutics often suffer from lack of specificity, resulting in toxicities to normal healthy tissues and poor therapeutic index. Antibody-drug conjugates (ADCs) constitute a therapeutic modality in which a cytotoxic agent is chemically linked to an antibody (Ab) that recognizes a tumor-associated antigen. The basic strategy underlying ADC technology is to combine the target selectivity of mAbs with the potency of cytotoxic agents, such as certain natural products and synthetic molecules, with the goal of generating therapeutic drugs that are highly efficacious but also safe. The ADC platform currently includes a growing repertoire of cytotoxic payloads, linker technologies and conjugation methods. Two ADCs have recently received FDA approval and more than 30 are in clinical development. This meeting aims to highlight advances in ADC research, clinical development and regulatory perspectives.

Anticancer antibodies  has created great interest in antibody-based therapeutics for hematopoietic malignant neoplasms and solid tumors. Given the likelihood of lower toxic effects of antibodies that target tumor cells and have limited impact on nonmalignant bystander organs vs small molecules, the potential increased efficacy by conjugation to radioisotopes and other cellular toxins, and the ability to characterize the target with clinical laboratory diagnostics to improve the drug's clinical performance, current and future antibody therapeutics are likely to find substantial roles alone and in combination therapeutic strategies for treating patients with cancer. Therapeutic antibodies have become a major strategy in clinical oncology owing to their ability to bind specifically to primary and metastatic cancer cells with high affinity and create antitumor effects by complement-mediated cytolysis and antibody-dependent, cell-mediated cytotoxicity (naked antibodies) or by the focused delivery of radiation or cellular toxins (conjugated antibodies).

Cancer immunotherapy—treatments that harness and enhance the innate powers of the immune system to fight cancer—represents the most promising new cancer treatment approach since the development of the first chemotherapies in the late 1940s. Because of the immune system’s extraordinary power, its capacity for memory, its exquisite specificity, and its central and universal role in human biology, these treatments have the potential to achieve complete, long-lasting remissions and cancer cures, with few or no side effects, and for any cancer patient, regardless of their cancer type. Immunotherapy is treatment that uses your body's own immune system to help fight cancer. These treatment modalities are all based on destroying cancer cells by burning them (irradiation), poisoning them (chemotherapy) or removing them (surgery). While they can effectively kill or remove cancer cells, the use of these treatments often is limited because large numbers of healthy cells also tend to be destroyed. This often results in extreme morbidity and/or disfigurement of the patients treated with them.

The first monoclonal antibodies were typically made entirely from mouse cells. One problem with this is that the human immune system will see these antibodies as foreign (because they’re from a different species) and will mount a response against them. In the short term, this can sometimes cause an immune response. In the long term, it means that the antibodies may only work the first time they are given; after that, the body’s immune system is primed to destroy them before they can provide treatment. This study presents a technology that generates stable, soluble, ultra-humanized antibodies via single-step CDR redundancy minimization. Lead clones demonstrated high stability, with affinity and specificity equivalent to, or better than, the parental immunoglobulin. This significantly lowered non-human sequence content, minimized t- and b-cell epitope risk in the final molecules and provided a heat map for the essential non-human CDR residue content of antibodies from disparate sources. Antibody humanization uses multiple sequence segments derived from variable (V) regions of unrelated human antibodies, unlike other technologies that typically use a single human V region framework as acceptors for complementarity determining regions (CDRs) from starting antibodies (typically rodent). Through careful selection of human sequence segments and the application of in silico tools, CD4+ T cell epitopes are avoided so the risk of immunogenicity is reduced compared to standard humanized antibodies whilst antibody affinity and specificity is maintained. Immunogenicity assessment technology is used to confirm T cell epitopes have been removed.

Antibiotics are a type of antimicrobials used in treatment and prevention of bacterial infections. They may inhibit or kill the growth of bacteria. Many antibiotics are also effective against protozoans and fungi; some are toxic to animals and humans also, even when given in therapeutic dosage. Antibiotics are not effective against viruses such as influenza or common cold, and may be harmful when taken inappropriately. Physicians must ensure the patient has a bacterial infection before prescribing antibiotics.

New diseases are arising worldwide and old diseases are re-emerging as Infectious agents evolve or spread, and as changes occur in ecology, socioeconomic conditions, and population patterns. Likewise, many diseases thought to be adequately controlled appear to be making a comeback. In developed countries, public health measures such as sanitation, sewage treatment, vaccination programs, and access to good medical care-including a wide range of antibiotics-have virtually eliminated “traditional” diseases such as diphtheria, whooping cough, and tuberculosis.

Antibacterial action generally falls within one of four mechanisms, three of which involve the inhibition or regulation of enzymes involved in cell wall biosynthesis, nucleic acid metabolism and repair, or protein synthesis, respectively. The fourth mechanism involves the disruption of membrane structure. Many of these cellular functions targeted by antibiotics are most active in multiplying cells. Since there is often overlap in these functions between prokaryotic bacterial cells and eukaryotic mammalian cells, it is not surprising that some antibiotics have also been found to be useful as anticancer agents.

Antibiotics, also known as antibacterials, are types of medications that destroy or slow down the growth of bacteria. In 1929, Alexander Fleming identified penicillin, the first chemical compound with antibiotic properties. Some of the common antibiotics are Penicillins, Cephalosporins, Carbapenems, Macrolides, Aminoglycosides, Quinolones, Sulfonamides and, Tetracyclines etc. General principles of antibiotic prescribing are use: First-line antibiotics first, Reserve broad spectrum antibiotics for indicated conditions only, prescribe antibiotics for bacterial infections if Symptoms are significant or severe.

The antibiotics market generated sales of US$42 billion in 2009 globally, representing 46% of sales of anti-infective agents (which also include antiviral drugs and vaccines) and 5% of the global pharmaceutical market1. However, the antibiotics market is maturing; it showed an average annual growth of 4% over the past 5 years, compared with a growth of 16.7% and of 16.4% for antiviral drugs and vaccines, respectively.

The cephalosporin class of antibiotics is the largest in terms of sales, generating $11.9 billion in 2009, led by sales of the latest generation of drugs in this class (cefcapene (Flomox; Shionogi), ceftriaxone (Rocephin; Roche) and cefuroxime (Zinnat; GlaxoSmithKline). This class represents 28% of the total antibiotic market, and sales showed a growth of 3.4% over the past 5 years. With sales of $7.9 billion and 19% of the antibiotic market share in 2009, the second largest drug class is the broad-spectrum penicillins, which showed a growth of 5% between 2005 and 2009. The third largest drug class — the fluoroquinolones — had sales of $7.1 billion in 2009, accounting for 17% of the antibiotic market in 2009, and also showed an average growth of 5% between 2005 and 2009. By contrast, as generic versions of an increasing number of macrolides — which had $4.8 billion in sales in 2009 — became available, sales of this class declined by 5% between 2007 and 2009. Overall, the rate of patent expiry of leading antibiotics in the market is set to increase, with several of the current top-selling products facing patent expiry between 2010 and 2016. These include levofloxacin (Levaquin; Johnson & Johnson), moxifloxacin (Avelox; Bayer/Merck) and linezolid (Zyvox; Pfizer), which are expected to lose patent protection in 2011, 2014 and 2016, respectively.

Prescribing doctors are, increasingly, using clinical trial data as a major source of information for evidence-based medicine for the treatment of infectious diseases, as in other clinical disciplines. However, it may be difficult to extract from these data the information that is needed for the management of the individual patient. At the same time, clinical trial data have been used, apparently satisfactorily, in the process of drug registration, and the pharmaceutical industry has spent increasingly large sums of money to satisfy the needs of this process. In the face of all these problems, changes in the way antibiotic clinical trials are designed and performed are clearly necessary, although this must not tip the balance so far as to render them less useful for those who currently derive greatest benefit from them.

Although the field of antibiotics is developing so rapidly as to render it almost kaleidoscopic, during recent months several topics of general interest have come into sharp focus. The subject of first consideration will include not only new drugs but also new forms of old drugs, as well as old drugs. Beyond this, I shall confine my discussion to two main items, bacterial resistance to antibiotics, and antibiotic toxicity. A variety of biological solutions have yet to be fully explored.

Antibiotics must be used judiciously in humans and animals because both uses contribute to the emergence, persistence, and spread of resistant bacteria. Resistant bacteria in food-producing animals are of particular concern. Food animals serve as a reservoir of resistant pathogens and resistance mechanisms that can directly or indirectly result in antibiotic resistant infections in humans. For example, resistant bacteria may be transmitted to humans through the foods we eat. Some bacteria have become resistant to more than one type of antibiotic, which makes it more difficult to treat the infections they cause. Preserving the effectiveness of antibiotic drugs is vital to protecting human and animal health.

Biopharmaceuticals is one of the fastest growing segments in the pharmaceutical industry. They have a vital use in the treatment of chronic diseases and also result in high profit margins for the drug developers. There are several therapeutic areas for which biopharmaceuticals are being investigated; these include oncology, metabolic disorders, viral infections, genetic disorders and immunological disorders

Antibody conjugates are a diverse class of therapeutics consisting of a cytotoxic agent linked covalently to an antibody or antibody fragment directed toward a specific cell surface target expressed by tumor cells. The notion that antibodies directed toward targets on the surface of malignant cells could be used for drug delivery is not new.

Next-generation sequencing (NGS) provides a quantitative approach to measuring the diversity and distribution of antibody libraries. It will introduce and enable researchers on how to design, analyze, and perform antibody NGS studies and how these can be applied for discovery and engineering of monoclonal antibodies from both synthetic and immune libraries. 

Therapeutic proteins and monoclonal antibodies (MAb) have transformed biotechnology and the pharmaceutical industry. Together they form the largest part of the rapidly growing biologics drug market. Protein-based drugs include blood factors, thrombolytic agents, hormones, hematopoietic growth factors, interferons, interleukins, tumor necrosis factor, and therapeutic enzymes. 

New biotherapeutics formats are flooding the discovery and development pipelines and with this comes an increasing need for better and faster characterization tools and strategies, and improved biomolecular and biophysical assays for the new biotherapeutics.

Protein Engineering is the process of creating helpful or profitable proteins and it research happens into the comprehension of collapsing and acknowledgment for protein plan standards. Analysts will have further point by point learning on In vitro development of proteins, Aspects of Biocatalysis, Advances in designing proteins for biocatalysis, Protein Engineered Biomaterials and many subjects. Computational Protein Engineering, Constructing practical biocatalysts and Growth of manufactured science are likewise normally utilized themes as a part of protein designing. The protein engineering business sector is estimated to develop at a CAGR of 15.7% to reach $1,463.0 million by 2020. There are very nearly 3000 individuals from 60-65 colleges in USA working for Protein Engineering and there are a few meetings & workshops like biomolecular designing gatherings, sub-atomic cell science workshops, protein engineering meetings, antibody engineering 2015 are conducting throughout the year globally.