Acute Coronary Syndrome (ACS)
Term including a range of clinical conditions resulting from insufficient blood supply to the heart muscle, including unstable angina and myocardial infarction.
A1 domain
Part of the von Willebrand Factor which binds to the glycoprotein (GP)Ib receptor on the surface of platelets.
Abciximab
Commercially available monoclonal antibody directed against the glycoprotein (GP)IIb/IIIa on the surface of platelets. It is used as an inhibitor of platelet aggregation and its trade name is ReoPro®.
ACR
American College of Rheumatology. Also the response criteria for achievement of clinical response after treatment with anti-rheumatoid therapeutics (i.e. ACR20).
Adalimumab
Fully human monoclonal antibody directed against TNFa.
ADAMTS13
Enzyme that cleaves von Willebrand Factor.
ADP receptor antagonists
Class of platelet activation inhibitors used for the management of thrombotic events.
Affinity
Measure of the binding strength between an antibody and its antigen.
Alternative scaffold therapeutics
Protein, other than an antibody, which is used as a backbone for displaying target specific binding sites for use as therapeutics.
Ankylosing spondilitis
Disease characterised by the chronic inflammation of the joints in the spine.
Antibody
Y shaped protein that is produced as the result of the introduction of an antigen into the body and that has the ability to specifically bind said antigen, triggering an immune response.
Antibody dependent cellular cytotoxicity
Mechanism of cell-mediated immunity whereby an effector cell of the immune system actively lyses a target cell that has been bound by specific antibodies.
Anticoagulant
Substance that prevents the clotting of blood.
Antigen
Any substance that can cause the production of antibodies.
Anti-IL-6R programme
Internal programme at Ablynx for the development of Nanobodies targeting the receptor for interleukin-6.
Anti-platelet agent
Substance that prevents the adhesion and aggregation of platelets, thereby preventing the formation of blood clots.
Anti-RANKL
Nanobodies or antibodies targeting RANKL.
Anti-Resorptive drugs
Drugs which reduce bone resorption.
Anti-thrombotic
Drug which prevents or reduces the formation of blood clots or thrombi.
ARC-1779
A peptide molecule (Aptamer) developed and owned by Archemix Corporation, targeting von Willebrand Factor.
Arterial thrombosis
Formation of blood clots (thrombi) in one or more arteries.
Assay
Procedure in molecular biology for testing and/or measuring the activity of a drug or biochemical in any organism or organic sample.
Atherosclerosis
Condition in which an artery wall thickens as the result of a chronic inflammatory reaction promoted by the build-up of fatty materials such as cholesterol.
Auranofin
Organogold compound, antirheumatic agent.
Avidity
Overall binding strength between an antibody and its antigen, determined by the number of binding sites between them.
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BAP
Bone Alkaline Phosphatase. An enzyme produced by osteoblasts. It has a role in the mineralisation of bone.
B-cell
Type of white blood cell that produces antibodies.
Biomarker
Characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.
Biparatopic Nanobodies
Nanobody constructs which bind to two different epitopes on the same target.
Bi-specific constructs
Nanobody constructs which bind to two different targets.
Bisphosphonates
Class of drugs that prevent and treat the loss of bone mass.
BLA
Biologic License Application. Application that the US Food and Drug Administration (FDA) must approve before a biologic can enter US market.
Black box warning
Type of warning that is used in the US on the package insert for prescription drugs that may cause serious adverse effects.
Blood-brain barrier
Separation of circulating blood and cerebrospinal fluid in the central nervous system.
Blue tongue disease
Non-contagious, insect-borne viral disease of ruminants, caused by the Bluetongue virus.
Bolus injection
Rapid injection of a drug, medication or other substance directly into a blood vessel.
Bone metastases
Tumours in the bones, arising from the spreading (metastasis) of a primary tumour from another organ.
Bone re-modelling
Life long process where old bone is removed (bone resorption) and new bone is added (bone formation).
Bone resorption
Process in which osteoclasts break down bone.
Boss patents
Patents belonging to the same patent family as the U.S. patent 4,816,397.
BSE
Bovine spongiform encephalopathy, a neurological disease commonly known as ‘mad cow disease’.
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Cabilly patents
Patents belonging to the same patent family as the U.S. patent 4,816,597.
Camelidae
Belonging to the class of mammals, this family comprises camels, dromedaries, llamas, alpacas, vicunas and guanacos.
Carotid endoarterectomy
Surgical procedure used to prevent stroke, by correcting stenosis in the common carotid artery.
Castleman’s disease
Very rare disorder characterised by non-cancerous growths (tumours) that may develop in the lymph node tissue at a single site or throughout the body and linked to overproduction of IL-6.
CD-20
Non-glycosylated phosphoprotein expressed on the surface of all mature B-cells.
CDR
Complementarity determining region. Relatively short amino acid sequence found in the variable domains of antigen receptors (e.g. immunoglobulins) that determine their specificity and make contact with a specific ligand.
Certolizumab pegol
Commercially available TNFa inhibitor.
Clinical Trial
Rigorously controlled test of a drug candidate or a new invasive medical device on humans.
Clopidogrel
Oral antiplatelet agent which targets the P2Y12 ADP receptor to inhibit thrombus formation.
Clotting or Coagulation cascade
Complex process consisting of a series of successive reactions resulting in the formation of a blood clot.
CMO
Contract Manufacturing Organisation.
Cohort
Group of subjects receiving treatment in a clinical trial.
Collagen
A group of naturally occurring proteins which are a natural constituent of connective tissue.
Complement activation
Activation of blood proteins leading to cell lysis or hypersensitivity reaction.
C-reactive protein
Protein found in the blood, the levels of which rise in response to inflammation.
CRO
Contract Research Organisation.
Crohn’s disease
Inflammatory disease of the intestines that may affect any part of the gastrointestinal tract from anus to mouth, causing a wide variety of symptoms.
CTX-1
Cross linked C-terminal telopeptides of type I collagen.
Degradation product of type I collagen, used as a marker for bone resorption.
Current Good Manufacturing Practice (cGMP)
cGMP standards are a part of the guarantee of the pharmaceutical quality of the drug and guarantee that drugs are made up and controlled in a consistent fashion, according to a standard of quality adapted to the considered use and in compliance with provisions on drugs.
CVE
Cerebrovascular Event or stroke.
Cytokine
Proteins that are secreted by specific cells of the immune system which carry signals locally between cells and thus have an effect on other cells.
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D
Dalton, a measure of M.W. or mass. One hydrogen atom has a mass of 1 Dalton. Proteins and other macromolecules are usually measured in kilo Daltons (1000 Dalton).
DAS 28
Disease Activity Score involving the count of 28 joints determining disease activity in rheumatoid arthritis.
Denosumab
anti-RANKL monoclonal being developed by Amgen.
Dimeric fusion protein
A molecule consisting of two binding arms linked to a protein backbone.
DMARDS
Disease-modifying antirheumatic drugs. A category of otherwise unrelated drugs defined by their use in rheumatoid arthritis to slow down disease progression.
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EMEA
European Agency for Evaluation of Medicinal Products.
Endarterectomy
Surgical procedure to remove the atheromatous plaque material, or blockage, in the lining of an artery constricted by the buildup of soft/hardening deposits.
Engineered antibody scaffolds
Antibody molecules that have been altered to have desired properties.
Epitope
Site on an antigen recognised by an antibody.
Etanercept
Commercially available TNFa inhibitor.
EULAR
European League Against Rheumatism.
European Winter-II patent
The European Patent 0 368 684.
Expression library
A library of DNA or RNA sequences in a format (for example, present in expression vectors) that allows said sequences to be expressed.
Expression systems
System specifically designed for the production of a gene product of choice.
Extracellular ligand
Protein which is secreted or located outside of a cell and which binds and activates a receptor.
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Fab
Fragment antigen binding portion of an antibody.
Factor VIII
An essential blood clotting factor.
Fc
Fragment crystallisation region, the tail region of an antibody that interacts with cell surface receptors and some proteins of the complement system. This property allows antibodies to activate the immune system.
Fc function
Function that is specifically mediated by the Fc region of an antibody molecule.
FDA
Food and Drug Administration, a Rockville, Maryland US based agency responsible for the drug approval process in the United States.
Flow cytometry
Analysis of biological material by detection of the light-absorbing or fluorescing properties of cells or cell fractions passing in a narrow stream through a laser beam.
Freedom to operate
Means that a particular action, such as testing or commercialising a product, can be done without infringing valid intellectual property rights of others.
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Germline
The body’s reproductive cells (egg or sperm). Germline DNA becomes incorporated into the DNA of every cell in the body of offspring.
Golimumab
Fully human monoclonal antibody directed against TNF.
GPlb-GPIX-GPV receptor complex
Glycoprotein complex on the cell surface of platelets, which binds von Willebrand Factor (also called GP1b receptor).
GPllb/llla inhibitor
A class of antiplatelet agents inhibiting GPIIb/IIIa on the cell surface of platelets.
G-Protein Coupled Receptors (GPCRs)
Cell membrane proteins of high medical and pharmacological importance.
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Haematopoiesis
The formation of blood cellular components.
Half-life
The length of time it takes for half of the drug molecules to get cleared from systemic circulation.
Hamers-I patent family
Patents covering the basic structure, composition, preparation and uses of Nanobodies.
Heavy chain antibody
Antibody which consists of two heavy chains only.
Hepatotoxicity
Treatment or intervention induced liver damage.
Heterodimeric cytokine
Cytokine consisting of two different subunits.
Homologous
Similar in linear sequence and structure.
Human single domain antibodies (dAbs)
Smaller fragments of mAbs being evaluated for their therapeutic potential (developed by Domantis Ltd., now owned by GlaxoSmithKline) that comprise either a mutated human heavy chain binding domain or a mutated human light chain binding domain.
Humanisation
Process by which a therapeutic protein of non-human origin is altered to more closely resemble a related human protein, intended to reduce the immunogenic potential of the drug.
Humate P
Freeze-dried human coagulation Factor VIII/ von Willebrand Factor complex.
Hydroxychloroquine
Antimalarial drug also used to reduce inflammation in the treatment of rheumatoid arthritis.
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Idiopathic Thrombocytopenic Purpura (ITP)
Autoimmune disease in which the body makes antibodies against its own platelets, leading to low platelet counts (thrombocytopenia).
IL-1 (Interleukin-1)
Cytokine involved in inflammatory diseases.
IL-6 (Interleukin-6)
Cytokine involved in inflammatory diseases.
Immunisation
Process by which an antigen is introduced in the body in order to raise an antibody response.
Immunogenic
Having the ability to raise an antibody response.
Immunoglobulin
See antibody.
IMPD
Investigational Medicinal Product Dossier. An application that a drug sponsor must submit to competent regulatory European agencies before beginning tests of a new drug on humans. The IMPD contains the plan for the study and is supposed to give a complete picture of the drug, including its structural formula, animal test results, and manufacturing information. The equivalent in the United States is called Investigational New Drug Application (IND).
Intravenous bolus
A relatively large dose of medication administered into a vein in a short period, usually within 1 to 30 minutes.
In vitro
In glass or plastic vessels rather than in living systems.
In vivo
In living systems.
Inflammatory bowel disease (IBD)
Group of chronic intestinal diseases characterised by inflammation of the bowel. The most common types of inflammatory bowel disease (IBD) are ulcerative colitis and Crohn’s disease.
Infliximab
A commercially available TNFa inhibitor.
Intravenous injection
The administration of a drug, medication or other substance directly into a vein.
Investigational New Drug Application (IND)
Investigational New Drug Application. An application that a drug sponsor must submit to FDA before beginning tests of a new drug on humans. The IND contains the plan for the study and is supposed to give a complete picture of the drug, including its structural formula, animal test results, and manufacturing information. The equivalent in Europe is called a Investigational Medicinal Product Dossier (IMPD).
Ion channels
Pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of all living cells.
Ischemic stroke
Dysfunction of brain tissue due to decreased blood supply to a part of the brain.
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kD
Kilo daltons (1000 Daltons).
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Leflunomide (a small molecule DMARDs)
Medication of the DMARD type used in active moderate to severe rheumatoid arthritis and psoriatic arthritis.
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M.W.
Molecular weight.
MACE
Major Adverse Cardiac Event. Criteria for evaluating cardiac treatments such as PCI.
McCafferty patent family
The European patents owned by the Medical Research Council, UK, that relate to certain aspects of the use of phage display techniques.
Methotrexate
Medication of the DMARD type used to treat cancer and auto-immune diseases.
Monoclonal Antibody (mAb)
An antibody produced in a laboratory from a single clone that recognises only one antigen.
Multiple myeloma
Cancer of the white blood cells known as plasma cells.
Multi-valent
Having more than one binding site.
Myocardial Infarction (MI)
Heart attack, caused by a severely reduced or stopped blood supply to part of the heart muscle (the myocardium).
Myocardial ischemia
A disease characterised by reduced blood supply to the heart muscle, usually due to atherosclerosis of the coronary arteries.
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Nanobody
Protein that is composed of one or more binding domains with the structural and functional characteristics of naturally occurring heavy chain variable domains (VHH’s) from Camelidae.
Nanobody Technology Platform
Ablynx’s know-how, expertise, patents and capabilities in relation to the discovery and development of Nanobodies for healthcare applications.
Nanoclone
Ablynx’s proprietary Nanobody discovery method based on the sorting of B cells originating from immunised lamas.
NExpedite
Novel proprietary half-life extension technology.
NRC
National Research Council, Canada.
NSAIDS
Nonsteroidal anti-inflammatory drugs.
NSTEMI
non-ST-elevation myocardial infarction.
NTX-1
Cross-linked N-telopeptides of type I collagen. Specific breakdown product of the type-I collagen found in bone cartilage, used as a marker of bone turnover.
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Occlusion
The state of something which is normally open, being closed.
Ocular delivery
Drug administration via the eyes.
Oligonucleotides
Short nucleic acid polymer.
Oral to systemic delivery
Systemic drug delivery after oral administration.
Oral-to-topical
Local effect of drug in the oral canal after oral administration.
Orphan disease
Rare medical condition.
Orphan drug
Drug treating a rare disease. The grant of orphan drug status by the authorities provides certain privileges, intended to stimulate the research, development and commercialisation of orphan drugs including market exclusivity of ten years in Europe and seven years in the United States.
Orphan Drug Designation
Acknowledgement of drug development and commercialisation of a therapeutic in a rare disease or condition by competent health authorities. Associated with several benefits for the pharmaceutical company during development and after registration including market exclusivity of ten years in Europe and seven years in the United States.
Osteoblast
Cells responsible for bone formation.
Osteoclast
Cells responsible for removal of bone issue (bone resorption).
Osteonecrosis of the jaw
Severe bone disease that affects the jaws.
Osteopenia
A condition where bone mineral density is lower than normal.
Osteoprotegerin (OPG)
Cytokine, which can inhibit the production of osteoclasts.
Osteosarcoma
A type of bone tumour.
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P1NP
Amino-terminal procollagen propeptides of type I collagen, used as a marker for bone formation.
P2Y12 ADP receptor
Protein on the surface of blood platelet cells and an important regulator in blood clotting.
Parathyroid hormone
Hormone secreted by the parathyroid glands.
PCI
Percutaneous coronary intervention. Surgical technique used to widen narrowed arteries. It is usually done by means of a balloon that, when deflated, is threaded into the affected area, then inflated compressing the plaque and dilating (widening) the narrowed coronary artery so that blood can flow more easily. This is often accompanied by inserting an expandable metal stent.
Pegylation
Addition of polyethylene glycol polymer chains to another molecule.
Peripheral artery occlusive disease (PAOD)
Condition that develops when the arteries that supply blood to the internal organs, arms, and legs become completely or partially blocked by a thrombus.
Phage display
Technique using recombinant DNA technology to create bacteriophages with a desired peptide or protein embedded in the surface of their protein coat. Agonists and antagonists of the target peptide can then be identified experimentally, enabling the engineering of antibodies and development of new drugs.
Pharmacokinetics
The study of the bodily absorption, distribution, metabolism, and excretion of drugs.
Pharmocodynamic
The action or effect of drugs on living organisms.
Phase I clinical trial
Clinical trial to test a new biomedical intervention in a small group of people for the first time to evaluate safety (for example, to determine a safe dosage range and to identify side-effects).
Phase II clinical trial
Clinical trial to study a new biomedical intervention in a larger group of people to determine efficacy and to further evaluate its safety.
PK profile
Pharmacokinetic profile.
Placebo
Medically inert substance given in connection with a controlled, double blinded clinical study.
Platelet
Also known as thrombocytes, are the smallest cells of the blood. They are involved in haemostasis and lead to the formation of blood clots.
Platelet adhesion
Binding of platelets to collagen, which is exposed after endothelial damage. Platelet adhesion is an early stage in the clotting cascade.
Platelet aggregation
The clumping together of platelets, one of the steps of the clotting cascade.
Prasugrel
New anti-platelet agent that targets the platelet ADP receptor P2Y12.
Pre-Clinical Trial
Laboratory test of a new drug candidate or a new invasive medical device on animals or cell cultures that is conducted to gather evidence justifying a clinical trial.
Protein
Molecule consisting of a chain of amino acids. Each protein has unique biological functions.
Psoriasis
Common skin disease characterised by thickened patches of inflamed, red skin covered with thick, silvery scales.
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RANK
Receptor Activator of Nuclear Factor kappa B. A membrane protein that is expressed on the surface of osteoclasts and is involved in their activation.
RANKL
Receptor Activator of Nuclear Factor kappa B ligand. A membrane molecule expressed on the surface of osteoblasts and stromal cells that activates osteoclasts.
Rheumatoid arthritis (RA)
Autoimmune disease that causes chronic inflammation of the joints, the tissue around the joints, as well as other organs in the body.
RICO
Ristocetin cofactor activity. A laboratory assay to evaluate von Willebrand Factor mediated platelet aggregation.
RIPA
Ristocetin induced platelet aggregation. A laboratory assay to evaluate von Willebrand Factor mediated platelet aggregation.
Rituxan
A chimaeric monoclonal antibody against the protein CD20, used in the treatment of many lymphomas, leukaemias, and some autoimmune disorders.
Rituximab
(see Rituxan)
RNA
Ribonucleic acid.
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Scaffold/fragment-based technologies
An alternative to full length antibodies. These include using fragments of classical antibodies such as Fab’s (as developed by Genentech/Roche and UCB Pharma), single domain antibodies of human origin (dAbs as developed by Domantis Ltd. (acquired by GlaxoSmithKline)), single domain antibodies of shark origin (as developed by Haptogen (acquired by Wyeth Pharmaceuticals)) and engineered antibody scaffolds (for example, SMIP’s as developed by Trubion.
Serum CTX-1
(see CTX-1)
Small molecule
Non-protein molecule drug.
SMIPs
Small Modular Immuno-Pharmaceuticals.
Spiegelmers
Novel, mirror-reversed RNA-like building blocks.
Splenectomy
Surgical procedure that partially or completely removes the spleen.
Stenotic atherosclerotic arteries
Narrowed arteries with atherosclerotic lesions.
Stroke
A stroke occurs when an artery carrying blood to the brain is either blocked by a blood clot or bursts.
Subcutaneous administration
Drug administration via injection just beneath the skin.
Sub-endothelial collagen
Collagen underneath the endothelium, which lines vessel walls.
Sulfasalazine
Medication of the DMARD type used to treat inflammatory bowel disease and rheumatoid arthritis.
Systemic administration
Administration of a therapeutic with a pharmacological effect on the entire body, e.g. via infusion or oral administration.
Systemic lupus erythematosus
Chronic autoimmune connective tissue disease that can affect any part of the body.
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T-cells
Type of white blood cells that play a central role in cell-mediated immunity.
Therapeutic antibody
Monoclonal antibody, typically humanised or fully human, used as a medicament.
Therapeutic peptide
Short protein consisting of at least two amino acids which has therapeutic activity.
Thrombocytopenia
Low platelet concentration in the blood.
Thrombolytic agent
Drug that is able to dissolve a clot (thrombus).
Thrombosis
Formation of a blood clot locally within a blood vessel.
Thrombotic microangiopathy
Category of pathologies that result in thrombosis in capillaries and arterioles.
Thrombotic thrombocytopenic purpura (TTP)
Thrombotic thrombocytopenic purpura (TTP or Moschcowitz syndrome) is a rare disorder of the blood-coagulation system, causing extensive microscopic thromboses to form in small blood vessels throughout the body (thrombotic microangiopathy).
Thrombus
Blood clot.
Ticlopidine
Antiplatelet drug in the thienopyridine family.
TIMI
Thrombolysis In Myocardial Infarction. A scoring system referring to levels of coronary blood flow assessed during percutaneous coronary angioplasty.
TNFa
Protein named Tumour Necrosis Factor-alpha produced by several of the body’s cell types, involved, amongst others, in systemic inflammation.
Transdermal delivery
Drug delivery through the skin.
Transgenic
Where cloned genetic material from one species or breed has been transferred to another.
Transient ischemic attack
Change in the blood supply to a particular area of the brain, resulting in brief neurologic dysfunction.
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UL-vWF
Ultra large von Willebrand Factor multimers.
Urine NTX-1
(see NTX-1)
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VH3-JH5 germline immunoglobulin sequence
Sequence of specific V and J regions of human immunoglobulin.
VHH
Variable or binding domain of a naturally occurring heavy chain antibody.
VIB
Flanders Institute for Biotechnology.
Von Willebrand Factor (vWF)
Substance in the blood that helps platelets stick to damaged vessel walls under high shear conditions, for example, in arteries.
VUB
Free University of Brussels.
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