Resurfacing of rodent antibodies

Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Recombinant dna technique included in method of making a...

Patent

Rate now

  [ 0.00 ] – not rated yet Voters 0   Comments 0

Details

4351721, 5303873, 5303877, 5303883, C12N 1500, C07K 1600, A61K 39395

Patent

active

056396414

ABSTRACT:
The invention relates to a method for providing, via resurfacing, humanized rodent antibodies that have improved therapeutic efficacy due to the presentation of a human surface in the variable region. In the method, (1) position alignments of a pool of antibody heavy and light chain variable regions is generated to give a set of heavy and light chain variable region framework surface exposed positions wherein the alignment positions for all variable regions are at least about 98% identical; (2) a set of heavy and light chain variable region framework surface exposed amino acid residues is defined for a rodent antibody (or fragment thereof); (3) a set of heavy and light chain variable region framework surface exposed amino acid residues that is most closely identical to the set of rodent surface exposed amino acid residues is identified; (4) the set of heavy and light chain variable region framework surface exposed amino acid residues defined in step (2) is substituted with the set of heavy and light chain variable region framework surface exposed amino acid residues identified in step (3), except for those amino acid residues that are within 5 .ANG.ngstroms of any atom of any residue of the complementarity determining regions of the rodent antibody; and (5) the humanized rodent antibody having binding specificity is produced.

REFERENCES:
patent: 4816397 (1989-03-01), Boss et al.
patent: 4816567 (1989-03-01), Cabilly et al.
patent: 5225539 (1993-07-01), Winter
Gorman et al., "Reshaping a Therapeutic CD4 Antibody", Proc. Natl. Acad. Sci., U.S.A., vol. 88, (1991) pp. 4181-4185.
Padlan, "A Possible Procedure for Reducing the Immunogenicity of Antibody Variable Domains While Preserving Their Ligand-Binding Properties", Molecular Immunology, vol. 28, No. 4/5, (1991) pp. 489-498.
Bobrzecka et al., "The Method of Controlled Rearrangement of Protein Disulphides and Its Use for Synthesis of Chimeric Immunoglobulin G", Immunology Letters, vol. 2, (1980) pp. 151-155.
Konieczny et al., "The Combination of IgM Subunits and Proteolytic IgG Fragments by Controlled Formation of Interchain Disulphides", Haematologia, vol. 14, No. (1), (1981) pp. 95-99.
Morrison et al., "Chimeric Human Antibody Molecules: Mouse Antigen-Binding Domains with Human Constant Region Domains", Proc. Natl. Acad. Sci., U.S.A., vol. 81, (1984) pp. 6851-6855.
LoBuglio et al., "Mouse/Human Chimeric Monoclonal Antibody in Man: Kinetics and Immune Response", Proc. Natl. Acad. Sci., U.S.A., vol. 86, (1989) pp. 4220-4224.
Martin et al., "Molecular Modeling of Antibody Combining Sites", Methods In Enzymology, vol. 203, (1991) pp. 121-153.
Martin et al., "Modeling Antibody Hypervariable Loops: A Combined Algorithm", Proc. Natl. Acad. Sci., U.S.A., vol. 86, (1989) pp. 9268-9272.
Morrison, "In Vitro Antibodies: Strategies for Production and Application", Annu. Rev. Immunol., vol. 10, (1992) pp. 239-265.
Waldmann, "Monoclonal Antibodies in Diagnosis and Therapy", Science, vol. 252, (1991) pp. 1657-1662 pp. 121-153.
Eduardo A. Padlan, A Possible Procedure for Reducing the Immunogenicity of Antibody Variable Domains While Preserving Their Ligand-Binding Properties, Molecular Immunology, vol. 28, pp. 489-498, 1991.
Stanfield et al. TibTelh vol. 12 1994 p. 275.

LandOfFree

Say what you really think

Search LandOfFree.com for the USA inventors and patents. Rate them and share your experience with other people.

Rating

Resurfacing of rodent antibodies does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Resurfacing of rodent antibodies, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Resurfacing of rodent antibodies will most certainly appreciate the feedback.

Rate now

     

Profile ID: LFUS-PAI-O-2157168

  Search
All data on this website is collected from public sources. Our data reflects the most accurate information available at the time of publication.