Immunology and Biotherapies

As of today, there are a total of 367 monoclonal antibodies either on the market or in development. 124 are fully human, 146 are humanized, 37 are chimeric, and 56 are murine, or mice antibodies. Of these 367, 38 are FDA approved since the first got through in 1986. 16 of those 38 have been approved in the last 5 years alone, which translates to 42%. We are gaining traction quickly, it seems.

 

Of the 38 approved mabs, 18 are humanized, 14 are fully human, 7 are chimeric, and only one is murine. The difference between the types is this: A chimeric mab is a cross between an animal and a human antibody engineered to react in a human setting. Humanized means that the antibody is mostly converted into a human form but originally came from an animal, usually a mouse. The term "fully human antibody" though is actually a bit misleading because in almost all cases it is not actually taken from a human. It is generally taken from a mechanism called a phage display, where human antibody genes are injected into a phage virus, which then expresses the antibodies on its coat. The best ones are then harvested from the virus. Think of it as microbiological agriculture.

 

Zooming back out to mabs in general, the top 10 bestselling mabs in 2014 account for $68B of the $78B total mab market last year. Number 1 is the fully human adalimumab, or Humira for rheumatoid arthritis, which looks set to eventually overtake Lipitor as the biggest blockbuster drug of all time. Humira was discovered via phage display, along with (nearly) all other fully human mabs on the market or in development.

Via Krishan Maggon

Abstract

Bispecific antibodies are on the cusp of coming of age as therapeutics more than half a century after they were first described. Two bispecific antibodies, catumaxomab (Removab®, anti-EpCAM × anti-CD3) and blinatumomab (Blincyto®, anti-CD19 × anti-CD3) are approved for therapy, and >30 additional bispecific antibodies are currently in clinical development. Many of these investigational bispecific antibody drugs are designed to retarget T cells to kill tumor cells, whereas most others are intended to interact with two different disease mediators such as cell surface receptors, soluble ligands and other proteins. The modular architecture of antibodies has been exploited to create more than 60 different bispecific antibody formats. These formats vary in many ways including their molecular weight, number of antigen-binding sites, spatial relationship between different binding sites, valency for each antigen, ability to support secondary immune functions and pharmacokinetic half-life. These diverse formats provide great opportunity to tailor the design of bispecific antibodies to match the proposed mechanisms of action and the intended clinical application.

Via Krishan Maggon

Highlights

 

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36 out of 39 approved monoclonal antibodies are native full-length IgG.

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Antibody engineering may further increase potency and improve the safety profile of conventional antibodies.

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Next generation of engineered antibodies may be even more efficient therapeutic molecules.

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18 multivalent engineered antibodies with promising preclinical results are now in clinical trials.

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In December 2014, blinatumomab became the first bispecific antibody approved in US.

 

The development of monoclonal antibody (mAb) technology has had a profound impact on medicine. The therapeutic use of first-generation mAb achieved considerable success in the treatment of major diseases, including cancer, inflammation, autoimmune, cardiovascular, and infectious diseases. Next-generation antibodies have been engineered to further increase potency, improve the safety profile and acquire non-natural properties, and constitute a thriving area of mAb research and development. Currently, a variety of alternative antibody formats with modified architectures have been generated and are moving fast into the clinic. In fact, the bispecific antibody blinatumomab was the first in its class to be approved by the US Food and Drug Administration (FDA) as recently as December 2014. Here, we outline the fundamental strategies used for designing the next generation of therapeutic antibodies, as well as the most relevant results obtained in preclinical studies and clinical trials.

Via Krishan Maggon