Donor specific antibody libraries

Abstract

The present invention concerns donor-specific antibody libraries derived from a patient donor who has suffered from, or is suffering from one or more diseases discussed herein. The present invention also concerns the method of making and using the donor-specific antibodies. The present invention further concerns the neutralizing antibodies obtained from the donor-specific antibody libraries and the methods of using these antibodies for the prevention/treatment of human disease.

1 . A vector collection comprising a repertoire of nucleic acid molecules encoding antibody light or heavy chains or fragments thereof, derived from a human patient donor who has suffered from, or is suffering from, a disease evoking antibody production to a target antigen, wherein said collection is identified with a unique nucleotide sequence barcode that is linked to and labels said nucleic acid molecules in the vector. 
     
     
         2 . The vector collection of  claim 1  comprising a repertoire of nucleic acid molecules encoding antibody light chains or fragments thereof. 
     
     
         3 . The vector collection of  claim 2  wherein the antibody light chains are λ chains. 
     
     
         4 . The vector collection of  claim 2  wherein the antibody light chains are κ chains. 
     
     
         5 . The vector collection of  claim 1  comprising a repertoire of nucleic acid molecules encoding antibody heavy chains or fragments thereof. 
     
     
         6 . The vector collection of  claim 1  wherein the barcode is a nucleotide sequence barcode is linked to and labels said nucleic acid molecules or incorporated in the vectors present in the collection, and/or linked to or incorporated in the nucleic acid molecules encoding the antibody light or heavy chains or fragments thereof such that it does not interfere with the expression of said nucleic acid molecules. 
     
     
         7 . The vector collection of  claim 6  wherein said nucleotide sequence barcode is a contiguous non-coding nucleotide sequence of one to about 24 nucleotides. 
     
     
         8 . The vector collection of  claim 7  wherein said nucleotide sequence barcode is linked to the 3′ or 5′ non-coding region of said nucleic acid molecules. 
     
     
         9 . The vector collection of  claim 6  wherein said nucleotide sequence barcode is a coding sequence of one or more silent mutations incorporated into the nucleic acid molecules encoding the antibody light or heavy chains or fragments thereof. 
     
     
         10 . The vector collection of  claim 6  wherein said nucleotide sequence barcode is in non-contiguous. 
     
     
         11 . The vector collection of  claim 10  wherein at least part of said non-contiguous nucleotide sequence is linked to or incorporated in the vectors present in the collection. 
     
     
         12 . The vector collection of  claim 10  wherein at least part of said non-contiguous sequence is incorporated into the nucleic acid molecules encoding the antibody light or heavy chains or fragments thereof such that it does not interfere with the expression of said nucleic acid molecules. 
     
     
         13 . The vector collection of  claim 1  wherein the barcode encodes peptide or polypeptide sequence. 
     
     
         14 . The vector collection of  claim 1  wherein the vectors are phagemid vectors. 
     
     
         15 . The vector collection of  claim 14  wherein the phagemid vectors contain a bacteriophage gene III and a stop codon between the nucleic acid molecules encoding antibody light or heavy chains or fragments thereof and the bacteriophage III gene. 
     
     
         16 . The vector collection of  claim 15  wherein the nucleotide sequence barcode is a non-coding contiguous nucleotide sequence inserted in the untranslated region following said stop codon. 
     
     
         17 . Host cells comprising the vector collection of  claim 1 . 
     
     
         18 . The host cells of  claim 16  which are  E. coli  host cells. 
     
     
         19 . A pooled vector collection comprising a plurality of vector collections according to any one of  claims 1  to  16  from different human donors, wherein different nucleotide sequence barcodes identify vectors or library members derived from the different donors. 
     
     
         20 . A pooled vector collection comprising a repertoire of nucleic acid molecules encoding antibody light or heavy chains or fragments thereof, derived from at least two human patient donors who have suffered from, or are suffering from, a disease evoking antibody production to a target antigen, wherein said collection is identified with a unique nucleotide sequence barcode that is linked to and labels said nucleic acid molecules in the vector. 
     
     
         21 . The vector collection of  claim 20  wherein the nucleotide sequence barcode is linked to and labels said nucleic acid molecules such that it does not interfere with the expression of said nucleic acid molecules. 
     
     
         22 . The vector collection of  claim 21  wherein said nucleotide sequence barcode is a contiguous non-coding nucleotide sequence of one to 24 nucleotides. 
     
     
         23 . The vector collection of  claim 22  wherein said nucleotide sequence barcode is linked to the 3′ or 5′ non-coding region of said nucleic acid molecules. 
     
     
         24 . The vector collection of  claim 21  wherein said nucleotide sequence is a coding sequence of one or more silent mutations incorporated into the nucleic acid molecules encoding the antibody light or heavy chains or fragments thereof. 
     
     
         25 . The vector collection of  claim 21  wherein said nucleotide sequence barcode is non-contiguous. 
     
     
         26 . The vector collection of  claim 25  wherein at least part of said non-contiguous nucleotide sequence is linked to or incorporated in the vectors present in the collection. 
     
     
         27 . The vector collection of  claim 25  wherein at least part of said non-contiguous sequence is incorporated into the nucleic acid molecules encoding the antibody light or heavy chains or fragments thereof such that it does not interfere with the expression of said nucleic acid molecules. 
     
     
         28 . The vector collection of any one of  claims 20 - 27  wherein the vectors are phagemid vectors. 
     
     
         29 . Host cells comprising the vector collection of any one of  claims 20 - 27 .