Antibodies

• Adal­i­mumab
• Alem­tuzumab
• Beva­cizumab
• Cetux­imab
• Deno­sumab
• Eculizumab
• Goli­mumab
• Inflix­imab
• Ipil­i­mumab
• Natal­izumab
• Nivolumab
• Omal­izumab
• Pembrolizumab
• Pertuzumab
• Ramu­cirumab
• Ranibizumab
• Ritux­imab
• Tocilizumab
• Trastuzumab
• Ustek­inumab

Adal­i­mumab

Adal­i­mumab (Humira®) is a human mono­clonal IgG1/​kappa anti­body indi­cated for the treat­ment of e.g. rheuma­toid arthritis, psori­atic arthritis, or Crohn’s disease. Humira®was the third tumor necrosis factor (TNF) ‑α inhibitor on the market, but the first fully human anti­body directed towards this target. Adal­i­mumab consists of a tetramer of two heavy and two light chains with one N‑glycosylation site per heavy chain. The patent of the orig­i­nator owned by AbbVie expired in 2016 in the US and in the EU in 2018; however, in the last few years AbbVie has secured about 70 (US) patents covering Humira® formu­la­tions, manu­fac­turing tech­niques and methods to treat multiple diseases. These addi­tional patents expire between 2022 and 2034 and AbbVie pursued liti­ga­tion to keep biosim­i­lars off the US market until at least 2022. Learn more

Alem­tuzumab

Alem­tuzumab (Lemtrada®) depletes circu­lating T- and B‑cells through anti­body-depen­dent cellular cytol­ysis and comple­ment-medi­ated lysis. Alem­tuzumab was orig­i­nally indi­cated for second-line treat­ment of chronic lympho­cytic leukemia (CLL), cuta­neous T‑cell lymphoma (CTCL) and normal T‑cell lymphoma under trade names Campath®, MabCam­path® and Campath-1H®. Currently it is indi­cated for the treat­ment of multiple scle­rosis as Lemtrada®. It is also applied for some condi­tioning regi­mens for bone marrow trans­plan­ta­tion, kidney trans­plan­ta­tion, and islet cell trans­plan­ta­tion. Basic patents for Lemtrada® already expired in 2017. Learn more

Beva­cizumab

Beva­cizumab (Avastin®) is a human­ized mono­clonal IgG1/​kappa anti­body that inhibits vascular endothe­lial growth factor A (VEGF‑A) and is used to treat various cancers including colorectal, lung, breast, kidney, and glioblas­tomas. Avastin® patents expired in 2019 in the US and will expire in the EU in 2022. Learn more

Cetux­imab

Cetux­imab (Erbitux®) is an epidermal growth factor receptor (EGFR) inhibitor indi­cated for the treat­ment of certain types of metastatic colorectal cancer, metastatic non-small cell lung cancer and head and neck cancer with or without radio­therapy or plat­inum-based chemotherapy. It is a chimeric mouse/​human mono­clonal anti­body. The main patents for cetux­imab expired in the EU in 2014 and in the US in 2016. Learn more

Deno­sumab

Deno­sumab (Prolia® Xgeva®) is a human mono­clonal anti­body indi­cated for the treat­ment of patients with osteo­porosis at high risk for frac­ture, giant cell tumor of bone, hyper­cal­cemia in malig­nancy and for the preven­tion of skeletal-related events in patients with bone metas­tases from solid tumors. It is the first FDA approved receptor acti­vator of nuclear factor kappa‑B ligand (RANKL) inhibitor. RANKL has been iden­ti­fied to affect the immune system and control bone regen­er­a­tion and remod­eling. Expiry dates of basic Prolia® patents related to the anti­body and treat­ment of patients range from 2017 to 2023 in US and from 2017 to 2021 in EU. Learn more

Eculizumab

Eculizumab (Soliris®) is a human­ized mono­clonal anti­body. It binds to the comple­ment compo­nent 5 (C5), which is a terminal mole­cule in the comple­ment cascade. Eculizumab inhibits the cleavage of C5 by C5 conver­tase into C5a and C5b and subse­quent gener­a­tion of the terminal comple­ment attack complex C5b‑9. Parox­ysmal nocturnal hemo­glo­bin­uria (PNH) patients are defi­cient in terminal comple­ment inhibitors. Eculizumab thus inhibits terminal comple­ment medi­ated intravas­cular hemol­ysis and there­fore the destruc­tion of erythro­cytes. Soliris® is indi­cated for treat­ment of patients with PNH to reduce hemol­ysis. It is also indi­cated for treat­ment of patients with atyp­ical haemolytic uremic syndrome (aHUS) to inhibit comple­ment medi­ated throm­botic micro-angiopathy. Patents on Soliris® will expire in USA in 2021 and in Europe in 2020. Learn more

Goli­mumab

Goli­mumab (Simponi®) is a fully human anti-tumor necrosis factor (TNF)-α IgG1қ mono­clonal anti­body. Simponi® is indi­cated in adults as an adjunct to methotrexate treat­ment for rheuma­toid arthritis, alone or as an adjunct to methotrexate treat­ment for active psori­atic arthritis and as a single agent for active anky­losing spondylitis and ulcer­a­tive colitis. Patents for Simponi® will expire in 2024 in US as well as in EU. Learn more

Inflix­imab

Inflix­imab (Remi­cade®) is a chimeric (mouse/​human) IgG1/​kappa mono­clonal anti­body. Like etan­er­cept and adal­i­mumab, inflix­imab is a TNF‑α blocker. Remi­cade® is indi­cated for treat­ment of Crohn’s disease, psori­atic arthritis, ulcer­a­tive colitis, psori­asis, anky­losing spondylitis, and rheuma­toid arthritis used together with methotrexate. The main patent of Remi­cade® expired in 2015 (EU) and in US in 2018. J&J (Janssen Biotech), the owner of the orig­i­nator mole­cule is trying to delay the market entry of biosim­i­lars with addi­tional patents, however, is strug­gling to defend their validity at court. Learn more

Ipil­i­mumab

Ipil­i­mumab (Yervoy®) is targeting the immune check­point T‑lym­pho­cyte-asso­ci­ated protein 4 (CTLA‑4). It was the first immune check­point inhibitor to be approved for the treat­ment of cancer. Yervoy® is indi­cated for unre­sectable or metastatic melanoma, as an adju­vant in the treat­ment of cuta­neous melanoma, to treat microsatel­lite-high or mismatch repair defi­cient metastatic colorectal cancer, hepa­to­cel­lular carci­noma, and in combi­na­tion with nivolumab (Opdivo®) for advanced renal cell carci­noma. Yervoy® patents will expire in the US in 2023 and in the EU in 2021. Learn more

Natal­izumab

Natal­izumab (Tysabri®) is a human­ized mono­clonal IgG4 anti­body directed against α4 inte­grin, a cellular adhe­sion mole­cule. It is the first anti­body in the class of selec­tive adhe­sion mole­cule inhibitors. Tysabri® is indi­cated as monotherapy for treat­ment of relapsing forms of multiple scle­rosis (MS) and in adult patients with moder­ately to severely active Crohn’s disease (CD) with evidence of inflam­ma­tion, which have had an inad­e­quate response or intol­er­ance to conven­tional CD ther­a­pies. The Tysabri® patents expired in 2015 in the EU as well as in the US. Learn more

Nivolumab

Nivolumab (Opdivo®) is a fully human mono­clonal IgG4 anti­body. Nivolumab blocks programmed cell death ligand 1 or 2 (PD-L1 or PD-L2) from binding to PD‑1, a protein on the surface of acti­vated T cells. Opdivo® is indi­cated, among other cancer types, as a first- or second- line treat­ment for inop­er­able or metastatic melanoma. This includes advanced non-small cell lung cancer, metastatic melanoma, advanced renal cell carci­noma, squa­mous cell carci­noma of the head and neck. Several patent fami­lies are filed, with expi­ra­tion dates of up to 2027 in US and 2026 in EU. Learn more

Omal­izumab

Omal­izumab (Xolair®) is a recom­bi­nant human­ized IgG1 kappa mono­clonal anti­body, which binds to free human immunoglob­ulin E (IgE) and to membrane-bound form of IgE (mIgE) on the surface of mIgE-expressing B lympho­cytes. Xolair® is indi­cated for moderate to severe persis­tent asthma and for chronic idio­pathic urticaria in patients who remain symp­to­matic despite H1 anti­his­t­a­mine treat­ment. Key patents on Xolair® already expired in 2017. Learn more

Pembrolizumab

Pembrolizumab (Keytruda®) is a human­ized mono­clonal IgG4 anti­body and is targeted to the cellular programmed cell death protein ‑1 (PD‑1). Programmed cell death ligand 1 or ligand 2 (PD-L1 or PD-L2) is upreg­u­lated on 40 – 50 % of melanomas and has limited expres­sion other­wise. Both ligands bind to PD‑1, a protein on the surface of acti­vated T‑cells. If PD-L1 binds to PD‑1, a T‑cell becomes inac­tive and inhib­ited from attacking a tumor.The inhibitory effect results from promo­tion of apop­tosis in antigen specific T cells while simul­ta­ne­ously blocking apop­tosis in suppressor T‑cells. Pembrolizumab binds to PD‑1, thus blocks PD-L1 or PD-L2 from binding to PD‑1, and T‑cells can again attack tumor cells. Keytruda® is indi­cated for, among other cancer types (more than 30 indi­ca­tions), melanoma, non-small cell lung cancer, head and neck squa­mous cell cancer, clas­sical Hodgkin lymphoma, gastric cancer, cervical cancer, hepa­to­cel­lular carci­noma, and primary medi­astinal large B‑cell lymphoma. Patents for Keytruda® have expiry dates of up to 2036 in US and 2028 in EU. Learn more

Pertuzumab

Pertuzumab (Perjeta®) is a recom­bi­nant human­ized mono­clonal anti­body that targets the dimer­iza­tion domain II of human epidermal growth factor 2 (HER2) expressed on the cell surface. When HER2 is over-induced and dimer­ized with HER3, cell growth accel­er­ates, which can lead to tumor forma­tion. Whereas similar mAb trastuzumab binds to domain IV of the extra­cel­lular segment of HER2 receptor, pertuzumab binds to domain II located on the oppo­site side. Dimer­iza­tion of HER2 / HER3 and acti­va­tion of signaling path­ways is thus prevented. Perjeta® is approved in combi­na­tion with Herceptin® (trastuzumab) and docetaxel chemotherapy for the treat­ment of HER2-posi­tive metastatic breast cancer not received prior anti-HER2 therapy or chemotherapy for metastatic disease. Patent expiry for Perjeta® will be in 2026 (US) and 2024 (EU). Learn more

Ramu­cirumab

Ramu­cirumab (Cyramza®) is a fully human mono­clonal IgG1 / kappa anti­body. Similar to beva­cizumab, ramu­cirumab inhibits angio­gen­esis (forma­tion of new blood vessels) by binding to a specific epitope on the extra­cel­lular domain of vascular endothe­lial growth factor receptor ‑2 (VEGFR‑2) and blocking the inter­ac­tion of VEGF‑A, VEGF‑C, or VEGF‑D with its recep­tors. Cyramza® is indi­cated for gastric cancer, gastro ‑oesophageal junc­tion adeno- carci­noma, metastatic colorectal cancer, non-small cell lung cancer that has spread to other parts of the body or in patients whose cancer involves muta­tions in EGFRs, and hepa­to­cel­lular carci­noma in patients with a high blood level of alpha feto­pro­tein. Cyramza® patents will expire in the US in November 2025 and in the EU in May 2023. Learn more

Ranibizumab

Ranibizumab (Lucentis®) is a human­ized mono­clonal anti­body frag­ment created from the same parent mouse anti­body as beva­cizumab. It is indi­cated for the treat­ment of neovas­cular (wet) age-related macular degen­er­a­tion, macular edema following retinal vein occlu­sion, diabetic macular edema, diabetic retinopathy, and myopic choroidal neovas­cu­lar­iza­tion. Ranibizumab binds to the receptor binding site of active forms of vascular endothe­lial growth factor A (VEGF‑A), including the biolog­i­cally active, cleaved form of this mole­cule, VEGF110. The binding of ranibizumab to VEGF‑A prevents the inter­ac­tion of VEGF‑A with its recep­tors (VEGFR1 and VEGFR2) on the surface of endothe­lial cells, reducing endothe­lial cell prolif­er­a­tion, vascular leakage, and new blood vessel forma­tion. The patents on Lucentis® will expire in the US in 2020 and in the EU in 2022. Learn more

Ritux­imab

Ritux­imab (Rituxan®, MabThera®) is a chimeric IgG1/​kappa mono­clonal anti­body targeting CD20, which is primarily found on the surface of B ‑cells. Ritux­imab destroys both normal and malig­nant B ‑cells that have CD20 on their surfaces, and is there­fore used to treat diseases, which are char­ac­ter­ized by having too many over­ac­tive or dysfunc­tional B ‑cells. Rituxan® is applied for treat­ment of many lymphomas and leukemias, trans­plant rejec­tion and some autoim­mune disor­ders. Rituxan® is also used off-label to treat diffi­cult cases of multiple scle­rosis, systemic lupus erythe­matosus and autoim­mune anemias. Rituxan® patents expired in 2013 in the EU and in 2016 in the US. Learn more

Tocilizumab

Tocilizumab (Actemra®) is a recom­bi­nant human­ized IgG1 mono­clonal anti­body targeting the interleukin‑6 receptor (IL-6R). Tocilizumab recog­nizes both the membrane-bound and the soluble form of IL-6R and thus is able to block IL‑6 func­tions. Actemra / RoActemra® is indi­cated for rheuma­toid arthritis, active poly-artic­ular, juve­nile idio­pathic arthritis, giant cell arteritis, cytokine release syndrome, and systemic scle­rosis. In Japan, it is also approved for treat­ment of Castleman’s disease. The patents on Actemra/​RoActemra® expired in US in 2015 and in Europe in 2017. Learn more

Trastuzumab

Trastuzumab (Herceptin®) is a human­ized mono­clonal anti­body that inter­feres with the human epidermal growth factor 2 (HER2)/neu receptor. The HER2 pathway promotes cell growth and cell divi­sion via HER2 receptor. When HER2 is over-induced and dimer­ized, cell growth accel­er­ates, which can lead to tumor forma­tion. Trastuzumab binds to domain IV of the extra­cel­lular segment of HER2 receptor preventing it from dimer­iza­tion and acti­va­tion of its signaling path­ways. Herceptin® is indi­cated for the treat­ment of HER2-posi­tive metastatic breast cancer patients. It is also approved for adju­vant treat­ment of HER2 over-expressing breast cancer and metastatic gastric cancer. Primary patents for Herceptin® expired in 2014 in EU and in US in 2019. Learn more

Ustek­inumab

Ustek­inumab (Stelara®) is an IgG1 kappa human mono­clonal anti­body. Ustek­inumab blocks inter­leukin IL-12 and IL-23, which acti­vate T helper cells (Th cells). Specif­i­cally it is targeting the p40 shared subunit of IL-12 and IL-23, which subse­quently cannot bind to their distinct recep­tors. Stelara® is indi­cated for treating patients with moderate to severe plaque psori­asis, and also to treat active psori­atic arthritis alone or with methotrexate. In 2016, it was also approved to treat Crohn’s disease. The patent protec­tion for Stelara® will be until 2023 in US and 2024 in EU. Learn more