|Title:||Human lysosomal proteins from plant cell culture|
|Abstract:|| A device, system and method for producing glycosylated proteins in plant culture, particularly proteins having a high mannose glycosylation, while targeting such proteins with an ER signal and/or by-passing the Golgi. The invention further relates to vectors and methods for expression and production of enzymatically active high mannose lysosomal enzymes using transgenic plant root, particularly carrot cells. More particularly, the invention relates to host cells, particularly transgenic suspended carrot cells, vectors and methods for high yield expression and production of biologically active high mannose Glucocerebrosidase (GCD). The invention further provides for compositions and methods for the treatment of lysosomal storage diseases.|
|Inventor(s):|| Shaaltiel; Yoseph (Kibbutz HaSolelim-Doar-Na HaMovil, IL), Baum; Gideon (Kibbutz Ayelet HaShachar-D.N. Upper Galilee, IL), Bartfeld; Daniel (Moran-Doar-Na Bikat Beit HaKerem, IL), Hashmueli; Sharon (Ramot-Naftali, IL), Lewkowicz; Ayala (Kfar-Vradim, IL) |
|Assignee:|| Protalix Ltd. (Carmiel, IL) |
|Filing Date:||Apr 06, 2011|
|Claims:||1. A pharmaceutical composition for the treatment of Gaucher's disease comprising lyophilized plant cells comprising a recombinant human glucocerebrosidase protein comprising the amino acid sequence as set forth in SEQ ID NO: 15, wherein said human glucocerebrosidase protein is glycosylated and comprises at least one exposed mannose, at least one fucose having an alpha (1-3) glycosidic bond and at least one xylose, and a pharmaceutically accepted carrier. |
2. The pharmaceutical composition of claim 1, wherein said human glucocerebrosidase protein has increased uptake into macrophages, in comparison with the corresponding affinity and uptake of a mammalian-cell-expressed recombinant human glucocerebrosidase protein.
3. The pharmaceutical composition of claim 1, wherein the main glycan structure of said glucocerebrosidase protein of said plant cell comprises at least one xylose residue and at least one exposed mannose residue, as measured by linkage analysis.
4. The pharmaceutical composition of claim 1, wherein said plant cell is a carrot cell.
5. The pharmaceutical composition of claim 4, wherein said plant cell is a carrot cell from suspension culture.
6. The pharmaceutical composition of claim 1 formulated for oral administration.
7. The pharmaceutical composition of claim 1, wherein said recombinant glucocerebrosidase protein has glucocerebrosidase biological activity.