<I forget what Fc type(s) MEDX chose. Do you recall if they picked more than one? Are all the antibodies the MEDX mice produce capable of inducing ADCC?>
As I recall most/all(?) of the MEDX ABs that I have seen reported in the literature are IgG1. However, my understanding is that MEDX’s mice are capable of producing all isotypes. Here is some info from the MEDX site.
HuMab-Mouse“Our HuMAb--Mouse transgenic strains contain key gene sequences from unrearranged human antibody genes that code for both the heavy and light chains of human antibodies.”
Kirin TC Mouse--“Through an exclusive partnership with the pharmaceutical division of Kirin Brewery Co., Ltd., we have access to the Kirin TC Mouse. Kirin has developed mice that contain complete sets of the variable and constant genes found in the corresponding natural human immunoglobulin loci. These mice are "transchromosomic," meaning that the mouse genes for creating antibodies have been inactivated and have been replaced by the human chromosomes containing all of the human antibody genes, including all heavy chain classes that encode all isotypes (IgG1-4, IgA1-2, IgD, IgM and IgE). The TC Mouse also has the ability to make fully human monoclonal antibodies. We have entered into a collaboration and license agreement, which provides for us to exchange with Kirin certain cross-licenses for each other's technology for the development and commercialization of human antibody products.” KM-Mouse --“Together with our partner, Kirin, we have developed the KM-Mouse, a crossbred mouse that combines the characteristics of our HuMAb-Mouse with Kirin's TC Mouse that retains the capability to produce all human antibody isotypes with an immune response we believe previously unseen in any human antibody producing mouse system.
HuMab-Mouse?It is unclear to me what isotypes these mice produce.
Kirin-TC?Looks like it makes all immunoglobulin isotypes.
KM-Mouse?A cross of the two mice. The benefits of this strain are unclear to me.
<Are all the antibodies the MEDX mice produce capable of inducing ADCC?> My understanding (as a nonimmunologist)?Immunoglobulin activation of ADCC varies with isotype. IgG1 is the most potent activator of ADCC. IgG2 and IgG4 are weaker activators of ADCC (unsure of the exact numbers). IgG3 can activate ADCC. I have seen patents from DNA/BIIB that have looked at IgG3 variants of Rituxin.
What it looks like is that MEDX mice can make all IgG isotypes. However, the most frequent isotype that MEDX and its partners have chosen to use is IgG1?I would presume due to it ability to activate ADCC, potentially an advantage in oncology settings. In non-oncology indications, activation of ADCC may not be necessary. For example, Tysabri is an IgG4. Also, HGSI has worked on IgG4 antibodies that antagonize CCR5.
<What do you think of MEDX in general?>
I own (and like) MEDX. Here are some positives.
1. Diverse reality stream on multiple antibody products with multiple high quality partners (PFE, J&J, AMGN, etc.). 2. Anti-CTLA-4. I think that anti-CTLA-4 has a good chance at approval. I’m not sure who will be first (or best) MEDX/BMY or PFE. 3. J&J phase III trials (CNTO148 and CNTO1275). 4. Genmab equity interest (recently reduced) and product royalties.
Couple of questions for you.
What does IIRC stand for?
<AMGN dumped most of Abgenix's research programs>?What is your source on this?
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