Abgenix: Was ist da dran ?? - 500 Beiträge pro Seite

[Matte]

Was machen die eigentlich?

WKN 915 298

Ich hoffe, ihr könnt mir da helfen.

ciao

Matte

[Greg1966]

Hallo Matte,
Abgenix hat als Technik die "Xenomaus" an der sie nun die alleinigen Rechte besitzt. Die Xenomaus hat z.T. ein menschliches Immunsystem, welches 100% humane Antikörper herstellt. Die Gene zur Produktion von Maus-Antikörpern wurden unterdrückt.
Damit hat Abgenix ein exzellentes Mittel in der Hand, um gegen beliebige Moleküle humane Antikörper herzustellen. Dies eröffnet ungeahnte Möglichkeiten für neue Medikamente. Siehe hierzu z.B. auch die Medikamente von Medimmune, welche derzeit einen durchschlagenden Erfolg haben und auch auf humanen Antikörpern basieren.
Für nähere Infos: www.abgenix.com

Im Anhang noch ein Ausschnitt von Abgenix:
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The company`s approach to generating human antibodies with fully human protein sequences is to use genetically engineered strains of mice in which mouse antibody gene expression is suppressed and functionally replaced with human antibody gene expression, while leaving intact the rest of the mouse immune system.  Rather than engineering each antibody product candidate, these transgenic mice capitalize on the natural power of the mouse immune system in surveillance and affinity maturation to produce a broad repertoire of high affinity antibodies.  By introducing human antibody genes into the mouse genome, transgenic mice with such traits can be bred indefinitely. Importantly, these transgenic mice are capable of generating human antibodies to human antigens because the only human products expressed in the mice (and therefore recognized as "self") are the antibodies themselves.  Any other human tissue or protein is thus recognized as a foreign antigen by the mouse and an immune response will be mounted. 

Abnormal production of certain human proteins, such as cytokines and growth factors or their receptors, have been implicated in various human diseases.   Neutralization or elimination of these abnormally produced or regulated human proteins with the use of human antibodies could ameliorate or suppress the target disease.   Therefore, the ability of these transgenic mice to generate human antibodies against human antigens could offer an advantage to drug developers compared with some of the other approaches described previously.  A challenge with this approach, however, has been to introduce enough of the human antibody genes in appropriate configuration into the mouse genome to ensure that these mice are capable of recognizing the broad diversity of antigens relevant for human therapies.

To make its transgenic mice a robust tool capable of consistently generating high affinity antibodies that can recognize a broad range of antigens, Abgenix equipped its XenoMouse with approximately 80% of the human heavy chain antibody genes and a significant amount of the human light chain genes. The complex assembly of these genes together with their semi-random pairing allows XenoMouse to recognize a diverse repertoire of antigen structures.  XenoMouse technology further capitalizes on the natural in vivo affinity maturation process to generate high affinity, fully human antibodies.  In addition, Abgenix has developed multiple strains of XenoMouse, each of which is capable of producing a different class of antibody to perform different therapeutic functions. Abgenix believes that its various XenoMouse strains will provide maximum flexibility for drug developers in generating antibodies of the specific type best suited for a given disease indication.

Abgenix believes that its XenoMouse technology offers the following advantages: (i) producing antibodies with fully human protein sequences; (ii) generating a diverse antibody response to essentially any disease target appropriate for antibody therapy; (iii) generating high affinity antibodies which do not require further engineering; (iv) enabling more efficient product development; and (v) providing flexibility in choosing manufacturing processes.
Recent advances in the technologies for creating and producing antibody products coupled with a better understanding of how antibodies and the immune system function in key disease states have led to renewed interest in the commercial development of antibodies as therapeutic products.  According to a recent survey by the Pharmaceutical Research and Manufacturers of America, antibodies account for over 20% of all biopharmaceutical products in clinical development.  In addition, eight monoclonal antibody products are being marketed as of December 31, 1998, for the treatment of a wide range of medical disorders.
Abgenix believes that, as products, antibodies have several potential clinical and commercial advantages over traditional therapies. These include:

faster product development;
fewer unwanted side effects as a result of high specificity for the disease target;
greater patient compliance and higher efficacy as a result of favorable pharmacokinetics;
delivery of various payloads, including drugs, radiation and toxins, to specific disease sites; and
ability to elicit a desired immune response.
Limitations of Current Approaches to Development of Antibody Products

Despite the early recognition of antibodies as promising therapeutic agents, most approaches thus far to developing them as products have met with a number of commercial and technical limitations.  Initial efforts were aimed at the development of hybridoma cells, which are immortalized mouse antibody-secreting B cells. Such hybridoma cells are derived from normal mouse B cells that have been genetically manipulated so that they are capable of reproducing over an indefinite period of time.  They are then cloned to produce a homogeneous population of identical cells which produce one single type of mouse antibody capable of recognizing one specific antigen ("monoclonal antibody").

While mouse monoclonal antibodies can be generated to bind to a number of antigens, they contain  mouse protein sequences and tend to be recognized as foreign by the human immune system.  As a result, they are quickly eliminated by the human body and have to be administered frequently.  When patients are repeatedly treated with mouse antibodies, they will begin to produce antibodies that effectively neutralize the mouse antibody, a reaction referred to as a Human Anti-Mouse Antibody ("HAMA") response.  In many cases, the HAMA response prevents the mouse antibodies from having the desired therapeutic effect and may cause the patient to have an allergic reaction. 

Recognizing the limitations of mouse monoclonal antibodies, researchers have developed a number of approaches to make them appear more human-like to a patient`s immune system.  For example, improved forms of mouse antibodies, referred to as "chimeric" and "humanized" antibodies, are genetically engineered and assembled from portions of mouse and human antibody gene fragments.  While such chimeric and humanized antibodies are more human-like, they still retain a varying amount of the mouse antibody protein sequence and, accordingly, may continue to trigger the HAMA response.  Additionally, the humanization process can be expensive and time consuming, requiring at least months and sometimes over a year of secondary manipulation after the initial generation of the mouse antibody.  Once the humanization process is complete, the remodeled antibody gene must then be expressed in a recombinant cell line appropriate for antibody manufacturing, adding additional time before the production of preclinical and clinical material can be initiated.   In addition, the combination of mouse and human antibody gene fragments can result in a final antibody product which is different in structure from the original mouse antibody, leading to a decrease in specificity or a loss in affinity.

[Klaus Meier]

Medarex ist doch in dem Bereich nicht wie schlechter aber der kurs noch 65 % niedriger wie seht ihr das ?