Replies to post #13006 on GTC Biotherapeutics (fka GTCB)

[quantumdot]

re: FOB mAbs

could you please clarify? in the first sentence you imply there is some irrational fear (amongst generic companies) that GTCs mAbs may be different and thus require a full clinical trial pathway and then in the second sentence you say that indeed GTCs mAbs are different and have different activity.

in effect you are saying that the chance of GTCs technology being used for production of FOB is very very low?

is that not the opposite of the investment/business case that Dew makes for this company?

[Lewis R Goudy]

>the goat mammary outfits GTC's Mabs with a glycolosation patern which conveys great activity than seen in the CHO Mabs. This is particularly important in ACCD<

And subject to revision. Waiting is, yet time is of
the essence:


Antibodies can exert anti-tumor effects via their ADCC (antibody-dependent cell-mediated cytotoxicity) activity or CDC (complement dependent cytotoxicity) activity. Antibodies are sugar chain-bound glycoproteins. It is known that an antibody's cytotoxic activity level can vary depending on the types and amounts of sugar chains that bind to the antibody. In particular, it has been reported that the amount of fucose binding to an antibody is strongly involved in the cytotoxic activity level. Furthermore, a method of producing a recombinant antibody not having fucose has been reported. Such method involves preventing an enzyme that catalyzes the binding of fucose to a sugar chain from being expressed upon antibody production in order to obtain an antibody with enhanced cytotoxic activity.

An object of the present invention is to provide a method for easily and reliably producing a recombinant protein wherein the binding of fucose is eliminated or decreases. In particular, an object of the present invention is to provide a method of producing an antibody wherein the binding of fucose is eliminated or decreases and whose cytotoxic activity is enhanced. Furthermore, another object of the present invention is to provide a host cell for producing such protein.

In a mechanism by which fucose binds to an antibody within an antibody-producing cell, it is known that GDP binds to fucose that has been incorporated into a cell. GDP-fucose is then incorporated into the Golgi apparatus and then the fucose of the GDP-fucose is transferred to N-acetylglucosamine that has been added as a sugar chain to protein within the Golgi apparatus. Specifically, the Fc region of an antibody molecule has two sites to which an N-glycoside-bound sugar chain binds. Fucose binds to the N-acetylglucosamine portion of an N-glycoside-bound sugar chain.

The present inventors have considered that disruption of fucose transporter genes on both chromosomes leads to inhibition of the incorporation of fucose into the Golgi apparatus, so that addition of fucose to an antibody can be inhibited. The present inventors have prepared a cell wherein fucose transporter genes on both chromosomes are disrupted and thus completed the present invention.

In the present invention, to satisfy conditions where the addition of fucose to an antibody is inhibited, it is not necessary that all the produced antibodies do not experience the addition of fucose thereto, but the proportion of protein to which fucose has been added should be decreased among antibody compositions.

The present invention will be described as follows.

[1] A cell, in which the expression of fucose transporter genes on both chromosomes is artificially suppressed. [2] The cell according to [1], in which the fucose transporter genes are disrupted. [3] The cell according to [1] or [2], which is an animal cell. [4] The cell according to [3], in which the animal cell is a Chinese hamster cell. [5] The cell according to [4], in which the animal cell is a CHO cell. [6] The cell according to any one of [2] to [5], in which gene disruption is carried out by homologous recombination using a gene targeting vector.

http://www.freshpatents.com/Method-of-producing-an-antibody-using-a-cell-in-which-the-function-of-fucose-transporter-is-inhibited-dt20080710ptan20080166756.php

[Lewis R Goudy]

>a Mab is just a Mab<

BTW that's not what I wrote (your italics clearly indicate
a direct quote). Please don't put words in my mouth to carry
your points--your mouth ought suffice.