Humanized Immunoglobulins and their production and use

摘要

The invention provides, inter alia, the use of first nucleotide sequences coding for framework regions from human acceptor Ig light and heavy chains and second nucleotide sequences coding for CDR's from a donor Ig in the production of expressible polynucleotides which encode a humanized immunoglobulin; which immunoglobulin is one obtainable by a method comprising: (a) comparing the framework or variable region amino acid sequences of the donor Ig light and heavy chains with corresponding sequences in a collection of human Ig chains;(b) selecting, to provide the human acceptor Ig light and heavy chain frameworks, sequences from the collection which have at least 65% identity with the respective donor framework sequences; and (c) combining CDR's from the donor Ig and frameworks from the selected acceptor sequences. The invention further includes the provision of humanized immunoglobulin, and in another aspect provides a method of designing a humanized immunoglobulin (Ig) chain having one or more CDR's from a donor Ig and a framework regions from a human Ig, said method comprising: comparing the framework or variable region amino acid sequence of the donor Ig light or heavy chain with corresponding sequences in a collection of human Ig chains; and selecting to provide the human Ig light or heavy chain framework one of the 3-5 most homologous sequences from the collection.