FIELD: medicine.
SUBSTANCE: method of producing an antigen-binding VH domain wherein an elongated CDR3 loop similar to a camel loop is absent, involves transformation of a mammal cell by a heavy-chain VH heterolocus. The locus contains a gene coding a variable area, at least containing one segment of VH gene, one segment of D gene not being camel's, one segment of J gene not being camel's, one invariable heavy chain region provided that any gene coding the invariable regions does not code a Sn1 functional domain. The segments of V, D and J genes are capable to recombination and formation of the VDJ coding sequence. The transformed cell is capable to express a heavy chain antibody only containing an antigen-binding VH domain and the invariable constant effector region without the functional domain Sn1. The cell is used for producing a transgene animal to be immunised with an antigen of concern. Further the cells or tissues expressing specific antibodies to the heavy chain antigen of concern are recovered; nucleic acid coding the VH domain of the specific heavy chain antibody only is recovered; and the specified antigen-binding VH domain is expressed. The specified VH domains can be used for production of fused proteins or binding complexes of monovalent, bivalent or polyvalent polypeptide.
EFFECT: invention allows producing antigen-specific human antibodies of any class, exhibiting high affinity.
11 cl, 26 dwg, 8 ex
| Title | Year | Author | Number | 
|---|---|---|---|
| SOLUBLE ANTIBODIES CONTAINING ONLY HEAVY CHAINS | 2010 | 
 | RU2528737C2 | 
| OBTAINING ANTIBODIES FROM SAME HEAVY CHAINS IN TRANSGENIC ANIMALS | 2007 | 
 | RU2435784C2 | 
| MICE THAT MAKE HEAVY CHAIN ANTIBODIES | 2010 | 
 | RU2603102C2 | 
| TRANSGENIC ANIMALS, OTHER THAN HUMANS, PRODUCING MODIFIED ANTIBODIES CONTAINING ONLY HEAVY CHAINS | 2017 | 
 | RU2762835C2 | 
| MOUSE PRODUCING BINDING PROTEINS CONTAINING VL-DOMAINS | 2011 |  | RU2612903C2 | 
| HUMANISED UNIVERSAL LIGHT CHAIN MICE | 2012 | 
 | RU2664232C2 | 
| MICE THAT PRODUCE BINDING PROTEINS CONTAINING V DOMAINS | 2011 | 
 | RU2750219C2 | 
| RESTRICTED IMMUNOGLOBULIN HEAVY CHAIN MICE | 2012 | 
 | RU2603090C2 | 
| CD3 BINDING ANTIBODIES | 2017 | 
 | RU2807216C2 | 
| HUMANIZED GNAWING ANIMALS THAT EXPRESS HEAVY CHAINS CONTAINING V DOMAINS | 2013 | 
 | RU2664185C2 | 
Authors
Dates
2010-09-10—Published
2005-07-22—Filed