Humanized antibodies

Abstract

The invention relates to novel humanized antibodies derived from the conventional antibody repertoire of species in the family Camelidae.

1 . An antibody comprising a camelid VH domain and a camelid VL domain, wherein an amino acid at one or more positions selected from the group consisting of H1, H5, H7, H11, H12, H13, H14, H29, H30, H37, H40, H48, H67, H68, H69, H71, H74, H77, H78, H80, H81, H82b, H83, H84, H85, H86, H89, H93, H94 and H108 of the camelid VH domain, according to Kabat, is replaced with an amino acid found at the corresponding position in a human VH domain sequence. 
     
     
         2 .- 8 . (canceled) 
     
     
         9 . An antibody comprising a camelid VH domain and a camelid VL domain, wherein the camelid VL domain is a camelid Vλ domain with homology to a human Vλ domain, and wherein an amino acid at one or more positions selected from the group consisting of L1, L2, L3, L5, L7, L8, L9, L11, L14, L15, L18, L17, L19, L20, L38, L39, L40, L42, L44, L46, L47, L49, L58, L59, L60, L66, L67, L69, L70, L71, L72, L74, L76, L78, L80, L81, L84, L103, L104 and L108 of the camelid Vλ domain, according to Kabat, is replaced with an amino acid found at the corresponding position in the human Vλ domain sequence. 
     
     
         10 .- 20 . (canceled) 
     
     
         21 . An antibody comprising a camelid VH domain and a camelid VL domain, wherein the camelid VL domain is a camelid Vκ domain with homology to a human Vκ domain, and wherein an amino acid at one or more positions selected from the group consisting of K1, K2, K3, K4, K7, K9, K11, K12, K13, K14, K15, K18, K19, K36, K39, K42, K43, K45, K46, K58, K63, K68, K70, K77, K78, K79, K80, K83, K100, K103, K104 and K106 of the camelid Vκ domain, according to Kabat, is replaced with an amino acid found at the corresponding position in the human Vκ domain sequence. 
     
     
         22 .- 37 . (canceled) 
     
     
         38 . A polynucleotide molecule encoding the antibody of  claim 1 . 
     
     
         39 . An expression vector comprising the polynucleotide molecule of  claim 38  operably linked to regulatory sequences that permit expression of the antibody in a host cell or cell-free expression system. 
     
     
         40 . A host cell or cell-free expression system containing the expression vector of  claim 39 . 
     
     
         41 . A method of producing a recombinant antibody, comprising culturing the host cell or cell-free expression system of  claim 40  under conditions which permit expression of the antibody; and recovering the expressed antibody. 
     
     
         42 . A polynucleotide molecule encoding the antibody of  claim 9 . 
     
     
         43 . An expression vector comprising the polynucleotide molecule of  claim 42  operably linked to regulatory sequences that permit expression of the antibody in a host cell or cell-free expression system. 
     
     
         44 . A host cell or cell-free expression system containing the expression vector of  claim 43 . 
     
     
         45 . A method of producing a recombinant antibody, comprising culturing the host cell or cell-free expression system of  claim 44  under conditions which permit expression of the antibody; and recovering the expressed antibody. 
     
     
         46 . A polynucleotide molecule encoding the antibody of  claim 21 . 
     
     
         47 . An expression vector comprising the polynucleotide molecule of  claim 46  operably linked to regulatory sequences that permit expression of the antibody in a host cell or cell-free expression system. 
     
     
         48 . A host cell or cell-free expression system containing the expression vector of  claim 47 . 
     
     
         49 . A method of producing a recombinant antibody, comprising culturing the host cell or cell-free expression system of  claim 48  under conditions which permit expression of the antibody; and recovering the expressed antibody.