Anti-a.beta. antibodies

A - Human Necessities – 61 – K

Patent

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Details

A61K 39/395 (2006.01) C07K 16/18 (2006.01) G01N 33/68 (2006.01)

Patent

CA 2451998

This invention provides variant 266 antibodies that are engineered to lack an N-glycosylation site within the CDR2 of the heavy chain, pharmaceutical compositions thereof, and polynucleotide sequences, vectors, and transformed cells useful to express the variant antibodies. The variants sequester soluble A.beta. peptide from humanbiological fluids and specifically bind an epitope contained withinposition 13-28 of the amyloid beta peptide A.beta. with significantly greater affinity than either mouse antibody 266 orhumanized 266 antibodies retaining N-glycosylation sites. The variant antibodies are useful for treatment or prevention of conditions and diseases associated with A.szlig., including Alzheimer's disease, Down's syndrome, cerebral amyloid angiopathy, mild cognitive impairment, and the like.

La présente invention se rapporte à des anticorps variants 266, qui sont conçus de façon à être dépourvus d'un site de N-glycosylation à l'intérieur de la région CDR2 de la chaîne lourde, à des compositions pharmaceutiques les contenant, ainsi qu'à des séquences polynucléotidiques, à des vecteurs d'expression, et à des cellules transformées utiles à l'expression des anticorps variants. Les variants piègent le peptide .ALPHA..beta. soluble à partir de fluides biologiques humains, et se lient spécifiquement à un épitope contenu aux positions 13 à 28 du peptide .ALPHA..beta. amyloïde, présentant une affinité sensiblement plus importante que les anticorps 266 murins ou les anticorps 266 humanisés retenant des sites de N-glycosylation. Les anticorps variants servent à traiter ou à prévenir des troubles et des maladies associées au .ALPHA..beta., notamment la maladie d'Alzheimer, le syndrome de Down, l'angiopathie amyloïde cérébrale, les déficiences intellectuelles légères, et d'autres troubles similaires.

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