An expression of the strength of the binding interaction between two molecules.
A substance capable of binding to a molecular target to initiate or enhance a physiological reaction.
A major feature of chronic persistent asthma, featuring mucus production, fibrosis of the tubes in the lungs, an increase in the amount of muscle in the tubes in the lungs and more blood vessels.
A condition caused by an overreaction of the immune system to foreign substances which are usually harmless.
A rheumatic disease that mainly affects the spine. Following inflammation, healing takes place which causes further bone growth. This leads to stiffening and may result in fusion of vertebrae.
A substance capable of binding to a molecular target to neutralize or counteract a physiological reaction induced by an agonist.
A protein produced by cells of the immune system, which specifically recognizes a target molecule known as an antigen. A key component of a body's defense mechanisms.
A molecule that binds to an antibody and is capable of stimulating specific antibodies in the body.
Programmed cell death.
A laboratory test to determine the strength of a solution, the proportion of a compound in a mixture, the potency of a drug or the purity of a preparation.
A condition in which individuals suffer from a widespread narrowing of the bronchial airways, which changes in severity over short periods (either spontaneously or under treatment) and leads to cough, wheezing and difficulty in breathing.
A disease that arises when the immune system mistakenly recognizes the body's own tissue as foreign and attacks it.
A type of virus that specifically infects bacteria.
Cancerous disease of the bone marrow resulting in unrestrained growth and proliferation of B-lymphocytes. B-cell malignancies or B-cell tumors are also known as leukemias (with circulating malignant B-cells) or lymphomas (characterized by solid masses of malignant cells in lymph nodes and other tissues).
The process of managing and analyzing large amounts of biological information.
The application submitted to the FDA, usually after completion of Phase III trials, which shows both clinical efficacy and safety of a biologic product in humans, and requests marketing approval in the United States.
A type of white blood cell that originates and develops in the bone marrow. B-cells can be stimulated to produce antibodies.
A naturally occurring protein that is required for the development of B-lymphocyte cells into mature B cells or plasma cells. In lupus, rheumatoid arthritis, and certain other autoimmune diseases, elevated levels of BLyS are believed to contribute to the production of autoantibodies — antibodies that attack and destroy the body's own healthy tissue.
A type of cancer that begins in the lining or covering of an organ that has often the ability to spread, or metastasize, to other areas of the body.
A cell surface receptor expressed in a wide variety of normal and malignant B-cells such as non-Hodgkin's lymphoma.
The treatment of disease by chemicals with a toxic effect on cells.
An antibody engineered from sequences of amino acids from different species.
Plaque psoriasis is the most common presentation of psoriasis and of all the patterns is the most likely to typically affect the areas of the elbows, knees, umbilicus, and lower back. It tends to be a relatively persistent or chronic pattern of psoriasis that can be improved with treatment but is difficult to clear completely with topical treatments alone. It is characterized by large flat areas (plaques) of psoriasis with typical silvery scale. These plaques may join together to involve very extensive areas of the skin particularly on the trunk and limbs. It is often accompanied by scalp and nail psoriasis.
A B-cell malignancy where the malignant cells are found in the bloodstream and bone marrow. It generally affects the elderly and tends to be less aggressive than non-Hodgkin's lymphoma and acute leukemia; however it still carries a significant mortality.
The replication of a segment of DNA.
A group of proteins in the blood serum that, when activated by, for example, antibodies, causes destruction of alien cells such as bacteria.
A chronic inflammatory disorder of the bowels.
Small protein molecules that are released by cells which affect the behavior of other cells and regulate biological processes.
The part of a cell that is contained within the cell membrane but excludes the cell nucleus.
Antibody fragments engineered to contain two antigen binding sites which can either be the same or different (bispecific).
The specific clinical condition for which a drug is intended to be used.
Genetic or biochemical processes that can be targeted with potential therapeutic drugs to prevent or treat disease. A disease target molecule is a molecule (often a protein) which is part of a biochemical pathway that is involved in a disease — the molecule may not be directly involved in the disease, but the modification of its function or activities may affect the disease or symptoms of the disease.
A chemical found primarily in the nucleus of cells. DNA carries the instructions for making all the structures and materials the body needs to function.
A feature of a clinical study in which neither the doctor nor the patient knows whether the patient is being administered the test drug or a control (drug or placebo).
Anti-TNF therapy for rheumatoid arthritis has a proven high degree of effectiveness. New studies suggest that earlier treatment can be as, or more, beneficial rather than waiting until patients have significant joint problems before ameliorating symptoms.
Several ways in which the immune system can remove foreign bodies, each being suited to a particular type of insult.
The outcomes measured in Phase III clinical trials that indicate that the test drug has the intended benefit.
A protein found on the surface of some cells and to which epidermal growth factor binds, causing the cells to divide. It is found at abnormally high levels on the surface of many types of cancer cells, so these cells may divide excessively in the presence of epidermal growth factor. Also known as ErbB1 or HER1.
A protein that attracts eosinophils into tissues where they degranulate and cause tissue damage. Eotaxin also acts to stimulate other types of white blood cells associated with inflammation. Eosinophils are white blood cells that destroy parasitic organisms and play a major role in allergic reactions. They secrete chemical mediators that can cause bronchoconstriction in asthma.
An epithelial adhesion molecule that is over-expressed with high frequency on most human carcinomas including breast, prostate, colon, lung, stomach, pancreas, head and neck, and ovarian cancer.
Part of the antigen that is recognized and bound by an antibody.
Refers to the cells that line the internal and external surfaces of the body.
European legislation governing and protecting European biotechnology.
The production of a protein from a cell or cellular system.
Relating to a biological process or reaction taking place outside of a living cell or organism.
Part of the U.S. Department of Health and Human Services Agency responsible for ensuring the safety and effectiveness of all drugs, biologics, vaccines, and medical devices. (The FDA is also responsible for food, animal feed, animal drugs, cosmetics, and radiation-emitting products.)
The proliferation of a type of tissue known as fibrous connective tissue. It normally occurs in the form of scar tissue.
The science related to the discovery and definition of the function of genes.
The standard for the design, conduct, performance, monitoring, auditing, recording, analyses, and reporting of clinical trials that provides assurance that the data and reported results are credible and accurate, and that the rights, integrity, and confidentiality of trial subjects are protected.
A protein that prevents skeletal muscle formation.
A functional unit of heredity, a segment or strand of DNA located in a specific site on a chromosome. A gene directs the formation of a protein.
Alteration of the DNA of a cell for purposes of research, as a means of manufacturing proteins, correcting genetic defects, or making alterations or improvements to plants and animals.
The total DNA content of an organism.
The body's reproductive cells (egg or sperm). Germline DNA becomes incorporated into the DNA of every cell in the body of offspring.
A compliance-monitoring program, through laboratory inspections and data audits, which assures the quality and integrity of test data.
A natural biological or synthetic process by which sugars are chemically attached to other molecules.
A receptor for a cytokine that stimulates the production and functional activity of granulocytes (white blood cells) and macrophages.
A quality assurance system required by authorities, for use in the manufacture of drugs.
A rare type of leukemia accounting for approximately 2% of the leukemia population. The incidence (US and EU combined) is approximately 1,800 patients per year with an estimated 300 deaths per year.
The process of using automated processes to enable the rapid isolation of antibodies to a large number of antigen targets simultaneously.
The process of using automated assays to quickly search through large numbers of substances for desired binding or activity characteristics.
Comprise human antibody frameworks into which binding sites from murine (mouse) or other non-human antibodies have been grafted. Also known as CDR grafted antibodies (Complementarity Determining Regions are the areas of an antibody molecule that interact/bind with antigens).
Relating to a type of immunity caused by free antibodies circulating in the blood.
A cell created artificially (i.e. not made within a living body system) by fusion of a tumor cell with a B-lymphocyte.
A disease of unknown cause.
The dominant class of immunoglobulin existing in the blood.
A biological molecule found in the body, responsible for triggering inflammation in a number of severe autoimmune and inflammatory disorders.
A T-lymphocyte-derived cytokine that appears to play a role in regulating inflammatory and immune responses.
A potent pro-inflammatory cytokine involved in T-cell (T-lymphocyte) and macrophage activation.
Something that gives rise to, or is capable of, stimulating a specific immune response.
Structurally related proteins endowed with known antibody activity (i.e. capable of recognizing and binding to an antigen). They can be categorized by structure and function into five different classes. Some immunoglobulins are carried on cell surfaces; others are free in the blood or lymph.
Capable of modifying or regulating one or more immune functions.
A hybrid molecule formed by joining a toxin to an antibody with the aim of targeting the toxin to a specific antigen, e.g., a tumor cell.
A response of living tissue to injury or infection.
In the natural or normal position.
Into a vein.
A compilation of the clinical and non-clinical data on the investigational product that is relevant to the study of the product in human subjects. Its purpose is to provide the investigators and others involved in the trial with the information to facilitate their understanding of the rationale for, and their compliance with, many key features of the protocol, such as the dose, dose frequency/interval, methods of administration, and safety monitoring procedures.
Latin for "in glass"; describing biological phenomena that are made to occur outside the living body; traditionally in a test tube.
Biological phenomena that are carried out in a living organism.
A form of diffuse lung disorder of unknown origin. Patients typically suffer shortness of breath and cough. Symptoms are restricted to the lungs and often progressive.
Molecules that exist in slightly different structural forms, but that may have a similar function.
A form of arthritis in children aged 16 or younger that causes inflammation and stiffness of joints for more than six weeks. Unlike adult rheumatoid arthritis, which is chronic and lasts a lifetime, children often outgrow juvenile rheumatoid arthritis although the disease can affect bone development in the growing child.
A molecule or compound capable of binding to a receptor.
A type of white blood cell.
A solution containing the contents of a lysed cell (a cell that has been broken apart).
Mammalian cells grown in tissue culture, normally selected for use by growth or other physiological characteristics.
A surface onto which a high density of probes have been applied in an ordered manner.
An antibody derived from a single clone of cells; all antibodies derived from such a group of cells have the same sequence of DNA.
The mediating template carrier between DNA and the production of proteins. The information from a single strand of DNA (a gene) is copied and transferred from the DNA by the construction of a complementary strand of RNA through a process known as transcription.
A disorder of the central nervous system of unknown cause in which the body's immune system attacks myelin in the brain and spinal cord. It results in multiple scars, or scleroses, on the myelin sheath, leading to impairment or loss of nerve function.
Relating to mice.
Lymphomas are malignancies of the lymphoid system and in the majority of cases the malignant cells are of B-cell origin. Hodgkin's disease is a subset with a particular histological appearance and generally has a good prognosis. All other lymphomas are referred to as Non-Hodgkin's Lymphoma. There are about 30 different sub-types which tend to be more aggressive and are associated with considerable mortality (19,000 deaths per year in the US). It is the second fastest growing cancer in the US after malignant melanoma.
Relating to any new or abnormal growth.
The branch of medicine dealing with the physical, chemical, and biological properties of tumors, including study of their development, diagnosis, treatment, and prevention.
Ligands/receptors for which a cellular function is as yet unknown.
A rapidly progressing cancer of the blood affecting the type of white blood cell known as lymphocytes.
The antigen binding site of an antibody.
A government grant to an inventor assuring him the sole right to make, use or sell his invention for a limited period.
A scientist that specializes in the branch of medicine concerned with the cause, origin, and nature of disease, including the changes occurring as a result of disease.
An agent that can cause disease.
A standard industry method for replicating DNA. A technique for rapidly reproducing many copies of a fragment of DNA for research or diagnostic purposes.
The abbreviation for bacteriophage, a virus that infects bacteria.
The study of drug action on living organisms.
The use of genetic information to predict the safety, toxicity, and/or efficacy of drugs in individual patients or groups of patients.
The study of the metabolism of drugs with particular emphasis on absorption, distribution in the body and elimination from the body.
The study of how drugs affect a living organism or cell.
This study includes the initial introduction of an investigational new drug or IND into humans. Phase I studies are typically closely monitored and may be conducted in patients or normal volunteer subjects. These studies are designed to determine the metabolism and pharmacologic actions of the drug in humans, the side effects associated with increasing doses, and, if possible, to gain early evidence of effectiveness. During Phase I, sufficient information about the drug's pharmacokinetics and pharmacological effects should be obtained to permit the design of well-controlled, scientifically valid Phase II studies. The total number of subjects and patients included in Phase I studies varies with the drug, but is generally in the range of 20 - 80. Phase I studies also include studies of drug metabolism, structure-activity relationships and mechanism of action in humans, as well as studies in which investigational drugs are used as research tools to explore biological phenomena or disease processes.
This study includes the controlled clinical activities conducted to evaluate the effectiveness of the drug for a particular indication or indications in patients with the disease or condition under study and to determine the common short-term side effects and risks associated with the drug. Phase II studies are typically well controlled, closely monitored and conducted in a relatively small number of patients, usually involving no more than several hundred subjects.
These studies are performed after preliminary evidence suggesting effectiveness of the drug has been obtained and are intended to gather additional information about effectiveness and safety that is needed to evaluate the overall benefit-risk relationship of the drug and to provide an adequate basis for physician labeling. Phase III studies usually include several hundred to several thousand subjects.
A pharmacologically inactive treatment used as a yardstick for measuring drugs.
The biological response engendered, taking into account the amount of substance administered. Often expressed as the ED50 for an agonist or an IC50 for an antagonist; the dose needed to elicit 50% of the maximum response.
A study that demonstrates an effect on a clinical endpoint that is either an accepted regulatory endpoint or is known to be highly predictive of that endpoint. Proof-of-concept needs to be carried out in patients with the disease in question.
A study that demonstrates an effect which results in a biological change which is closely related to the proposed mechanism of action and known to be associated with disease activity in patients. Proof-of-principle can also be carried out in patients or healthy volunteers using appropriate challenge agents provided that a clear link can be established between the effect and the target disease.
Large molecules made of smaller biological units known as 'amino acids'. Proteins are responsible for most of the function and much of the structure of living things, including humans.
A detailed analysis of a particular protein, encompassing structure and function studies, in a healthy and disease context, also known as proteomics.
A chronic skin condition characterized by inflamed, red, raised areas that develop silvery scales.
Arthritis associated with psoriasis (a chronic skin disease in which scaly pink patches form on the elbows, knees, scalp, and elsewhere), and often affecting the joints of the hands.
The internal and external audit of Quality Control systems, to comply with all legal requirements necessary for releasing materials and validation of documentation. Covers GLP or (Good Lab Practice) and GCP (Good Clinical Practice).
Defined SOPs, tests, analysis, and other action required to control output, e.g. purity, stability and final product. Includes systems to implement GMP.
Typically a protein located on or inside a cell with which a different molecule known as a ligand may interact to produce or inhibit a biological response.
A condition characterized by chronic inflammation and gradual destruction of the joints.
A large complex molecule that synthesizes protein.
A decrease in muscle mass.
A single polypeptide chain comprising the variable domains of an antibody heavy chain and an antibody light chain joined together by a flexible linker.
Blood plasma (the clear yellowish fluid portion of blood in which the blood cells are suspended) from which the clotting factors have been removed.
An inflammatory disorder of the airways associated with airflow obstruction. Although therapy controls the disease in the majority of patients, it is recognized that a subgroup of asthmatics, approximately 10%, show reduced responsiveness to standard therapy, experience greater morbidity, and a lower quality of life than those asthmatics whose disease is adequately controlled by therapy. Despite the use of high doses of inhaled and oral corticosteroid anti-inflammatory drugs, this group suffers airflow obstruction that is either non-reversible or at best, difficult to reverse.
A serious, chronic, autoimmune disorder characterized by periodic episodes of inflammation of, and damage to the joints, tendons, other connective tissues, and organs, including the heart, lungs, blood vessels, brain, kidneys, and skin.
The link between the structure of a molecule and its function.
Beneath the skin.
A target molecule for therapeutic intervention.
A family of multifunctional biological molecules, excessive production of which is associated with fibrosis and scarring (see fibrosis above).
Belongs to the 'cytokine' family of biological molecules. TNFα is responsible for increasing tissue damage in inflammatory disorders such as rheumatoid arthritis.
A scientist trained to examine the nature of the adverse effects of chemicals on living organisms and assess the probability of their occurrence. Toxicology is the study of symptoms, mechanisms, treatments and detection of biological poisoning. The chief criterion regarding the toxicity of a chemical is the dose, i.e., the amount of exposure to the substance.
TRAIL Receptor 1 or TRAIL-R1 and similarly, TRAIL Receptor 2 or TRAIL-R2 or TNF-Related Apoptosis-Inducing Ligand
Proteins expressed on the surface of a number of cancer cells, which when triggered, induce apoptosis or cell death.
The synthesis of mRNA using a DNA template.
Containing genetic material artificially transferred from another species.
The process by which proteins are formed using the sequence information encoded in mRNA.
VEGFRs are membrane receptors to which the VEGF ligand binds; VEGFR-2 is expressed on endothelial cells, and is thought to be principally responsible for angiogenesis and for the proliferation of endothelial cells.
A virtual business model is one in which a company hires external contractors or workforce to carry out its activities as opposed to hiring full time employees.