Methoxy polyethylene glycol-epoetin beta is the active ingredient of a drug marketed by

Hoffmann-La Roche F. Hoffmann-La Roche AG, commonly known as Roche, is a Swiss multinational healthcare company that operates worldwide under two divisions: Pharmaceuticals and Diagnostics. Its holding company, Roche Holding AG, has shares listed on the SIX ...

under the brand name Mircera. Mircera is a long-acting

erythropoietin receptor The erythropoietin receptor (EpoR) is a protein that in humans is encoded by the ''EPOR'' gene. EpoR is a 52kDa peptide with a single carbohydrate chain resulting in an approximately 56-57 kDa protein found on the surface of EPO responding cells. ...

activator (CERA) indicated for the treatment of patients with

anaemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, th ...

associated with chronic kidney disease. It is the first approved, chemically modified

erythropoiesis-stimulating agent Erythropoiesis-stimulating agents (ESA) are medications which stimulate the bone marrow to make red blood cells. They are used to treat anemia due to end stage kidney disease, chemotherapy, major surgery, or certain treatments in HIV/AIDS. In th ...

(ESA). Mircera is supplied as a solution in pre-filled syringes for intravenous or subcutaneous administration. Mircera was approved for use in Europe in July 2007 by the European Commission, in September 2007 by the

Swissmedic The Swiss Agency for Therapeutic Products (Swissmedic) is the Swiss surveillance authority for medicines and medical devices, registered in Bern. It began operations on 1 January 2002 as successor of ''Interkantonale Kontrollstelle für Heilmittel ...

, and in November 2007 by the

U.S. Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

for use in the United States. Methoxy polyethylene glycol-epoetin beta is made from

erythropoietin Erythropoietin (; EPO), also known as erythropoetin, haematopoietin, or haemopoietin, is a glycoprotein cytokine secreted mainly by the kidneys in response to cellular hypoxia; it stimulates red blood cell production (erythropoiesis) in the bo ...

by chemically linking the N-terminal amino group or the ε-amino group of any

lysine Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. It contains an α-amino group (which is in the protonated form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −C ...

present in the protein with methoxy polyethylene glycol butanoic acid. The average

molecular weight A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioch ...

is approximately 60 kDa. The drug stimulates

erythropoiesis Erythropoiesis (from Greek 'erythro' meaning "red" and 'poiesis' "to make") is the process which produces red blood cells (erythrocytes), which is the development from erythropoietic stem cell to mature red blood cell. It is stimulated by decrea ...

by interacting with the erythropoietin receptor on progenitor cells in the

bone marrow Bone marrow is a semi-solid tissue found within the spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It is composed of hematopoietic ce ...

. It has a reduced receptor binding activity compared to other ESAs and but retains in vivo activity due to an extended serum half-life. It has an ''in vivo'' half-life of around 135 hours (5.6 days) as compared to

darbepoetin alfa Darbepoetin alfa (INN) is a re-engineered form of erythropoietin containing 5 amino acid changes (N30, T32, V87, N88, T90) resulting in the creation of 2 new sites for N-linked carbohydrate addition. It has a 3-fold longer serum half-life compare ...

which has a half life of around 21 to 70 hours, the half life of which is three times that of the naturally occurring erthropoietin in the body. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health ...

Patent infringement claims

A U.S. Federal Appeals Court ruled 15 September 2009 that Mircera infringes a patent held by

Amgen Inc. Amgen Inc. (formerly Applied Molecular Genetics Inc.) is an American multinational biopharmaceutical company headquartered in Thousand Oaks, California. One of the world's largest independent biotechnology companies, Amgen was established in T ...

The court refused to lift an

injunction An injunction is a legal and equitable remedy in the form of a special court order that compels a party to do or refrain from specific acts. ("The court of appeals ... has exclusive jurisdiction to enjoin, set aside, suspend (in whole or in pa ...

entered in the fall of 2008 which barred Roche from selling Mircera in the United States. However, the injunction has since expired and Mircera is available on the US market since 2015.

Use in sports

Mircera can reportedly replace traditional EPO drugs as

blood doping Blood doping is a form of doping in which the number of red blood cells in the bloodstream is boosted in order to enhance athletic performance. Because such blood cells carry oxygen from the lungs to the muscles, a higher concentration in the bl ...

agent in endurance sports. The drug appears to fall under section S2 of the list of substances officially prohibited - in competition and out of competition - in

France France (), officially the French Republic ( ), is a country primarily located in Western Europe. It also comprises of Overseas France, overseas regions and territories in the Americas and the Atlantic Ocean, Atlantic, Pacific Ocean, Pac ...

and by the

World Anti-Doping Agency The World Anti-Doping Agency (WADA; french: Agence mondiale antidopage, AMA) is a foundation initiated by the International Olympic Committee based in Canada to promote, coordinate, and monitor the fight against drugs in sports. The agency's key ...

. On July 17, 2008, Italian bicycle racer

Riccardo Riccò Riccardo Riccò (born 1 September 1983) is an Italian professional road bicycle racer, who is suspended from all competition until 2024. He was previously ejected from the 2008 Tour de France for doping violations and suspended. Riccò returned ...

was disqualified from the

Tour de France The Tour de France () is an annual men's multiple-stage bicycle race primarily held in France, while also occasionally passing through nearby countries. Like the other Grand Tours (the Giro d'Italia and the Vuelta a España), it consists ...

after reports that a urine sample tested positive for Mircera. There had not previously been any public acknowledgment that a test for the new drug was being administered, or had even been developed yet. The Tour de France testing was done under the auspices of the

French Cycling Federation The Fédération Française de Cyclisme (''FFC'') or French Cycling Federation is the national governing body of cycle racing in France. The FFC is a member of the UCI and the UEC. In February 2009, David Lappartient was elected for a four-ye ...

and the

French Anti-Doping Agency The French Anti-Doping Agency (, AFLD) is an independent public authority formed in 2006 and charged with ensuring that participants in sports in France do not violate rules regarding doping. As a national anti-doping organization ( NADO), the A ...

, not the

Union Cycliste Internationale The ''Union Cycliste Internationale'' (UCI; ; en, International Cycling Union) is the world governing body for sports cycling and oversees international competitive cycling events. The UCI is based in Aigle, Switzerland. The UCI issues racing ...

References

{{Cytokine receptor modulators Antianemic preparations Erythropoiesis-stimulating agents World Anti-Doping Agency prohibited substances Hoffmann-La Roche brands

Patent infringement claims

Use in sports

See also

References