Humanized anti-CEA T84.66 antibody and uses thereof

Drug – bio-affecting and body treating compositions – Immunoglobulin – antiserum – antibody – or antibody fragment,... – Structurally-modified antibody – immunoglobulin – or fragment...

Reexamination Certificate

Rate now

  [ 0.00 ] – not rated yet Voters 0   Comments 0

Details

Reexamination Certificate

active

11077978

ABSTRACT:
Embodiments of the present invention utilize a more efficient CDR grafting technique to generate humanized versions of the T84.66 antibody. The technique used to generate these antibodies utilizes crystallographic structural data to select an immunoglobulin framework having maximum structural overlap with a non-human donor molecule. This technique was used to develop humanized T84.66 antibodies exhibiting in vitro binding affinity and specificity for carcinoembryonic antigen (CEA) nearly identical to that of T84.66 and the ability to specifically target tumors expressing CEA in vivo.

REFERENCES:
patent: 5639641 (1997-06-01), Pedersen et al.
patent: 6639055 (2003-10-01), Carter et al.
Bowie et al, Science, 247:1306-1310, 1990, p. 1306. col. 2).
Gussow et al (1991, Methods in Enzymology 203:99-121).
(Rudikoff et al, PNAS, USA. 1982. 79: 1979).
Neumaier et al. (1990, Cancer Research 50:2128-2134).
Wong et al. (1998, J. Nucl. Med. 39(12):2097-104) (abstract only).
Willuda et al. (1999, Cancer Research 59:5758-5767).
Hu et al. Minibody: A Novel Engineered Anti-Carcinoembryonic Antigen Antibody Fragment (Single-Chain Fv-CH3) Which Exhibits Rapid, High-Level Targeting of Xenografts, Cancer Research 1996, vol. 56:3055-3061.
Wong et al. A phase I trial of90Y-Anti-Carcinoembryonic Antigen Chimeric T84.66 Radioimmunotherapy with 5-Fluorouracil in Patients with Metastatic Colorectal Cancer, Clinical Cancer Research, Dec. 2003, vol. 9, 5842-5852.
Beatty, J.D., et al. “Preoperative imaging of colorectal carcinomas with111In-labeled anti-carcinoma antigen monoclonal antibody.”Cancer Res.46:6494-6502 (1986).
Bebbington, C., et al. “High-level expression of a recombinant antibody from myeloma cells using a glutamine synthetase gene as an amplifiable selection marker.”Biotechnology10:169-175 (1992).
Berman, H.M., et al. “The Protein Data Bank,”Nucleic Acids Res.28:235-242 (2000).
Bernstein, F., et al. “The Protein Data Bank: A computer-based archival file for macromolecular structures,”J. Mol. Biol.112:535-542 (1977).
Blumenthal, R.D., et al. “Carcinoembryonic antigen antibody inhibits lung metastasis and aguments chemotherapy in a human colonic carcinoma xenograft.”Cancer Immunol. Immunother, 54:315-327 (2005).
Bruggemann, M., et al. “Human antibody production in transgenic mice: expression from 100 kb of the human IgH locus.”Eur. J. Immunol.21:1323-1326 (1991).
Carmichael, J.A., et al. “The crystal structure of an anti-CEA scFv diabody assembled from T84.66 scFvs in V(L)-to-V(H) orientation: implications for diabody flexibility.”J. Mol. Biol.326:341-351 (2003).
Chothia, C., et al. “Canonical structures for the hypervariable regions of immunoglobulins.”J. Mol. Biol.196:901-917 (1987).
D'Argenio, D.Z., et al. “A program package for simulation and parameter estimation in pharmacokinetic systems.”Comput. Programs Biomed.9:115-134 (1979).
Eigenbrot, C., et al. “X-ray structures of the antigen-binding domains from three variants of humanized anti-p185HER2antibody 4D5 and comparison with molecular modeling.”J. Mol. Biol.229:969-995 (1993).
Eigenbrot, C., et al. “X-Ray structures of fragments from binding and nonbinding versions of a humanized anti-CD18 antibody: structural indications of the key role of VH residues 59 to 65.”Proteins18:49-62 (1994).
Foote, J., et al. “Antibody framework residues affecting the conformation of the hypervariable loops.”J. Mol. Biol.224:487-499 (1992).
Gibrat, J.F., et al. “Surprising similarities in structure comparison.”Curr. Opin. Struct. Biol.6:377-385 (1996).
Horton, R.M., et al. “Engineering hybrid genes without the use of restriction enzymes: gene splicing by overlap extension.”Gene77:61-68 (1989).
Huang, E.H., et al. “CEA-based vaccines.”Expert Rev. Vaccines1:49-63 (2002).
Imikare, T., et al. “Generation, immunologic characterization and antitumor effects of human monoclonal antibodies for carcinoembryonic antigen.”Int. J. Cancer108:564-570 (2004).
Johnson, G., et al. “Kabat database and its applications: future directions.”Nucleic Acid Res.29:205-206 (2001).
Jones, P.T., et al. “Replacing complementarity-determining regions in a human antibody with those from a mouse.”Nature321:522-525 (1986).
Laemmli, U. “Cleavage of structural protein during the assembly of the head of bacteriophage T4.”Nature227:680-685 (1970).
Low, N.M., et al. “Mimicking somatic hypermutation: affinity maturation of Antibodies Displayed on Bacteriophage Using a Bacterial Mutator Strain.”J. Mol. Biol.260:359-368 (1986).
MacCallum, R.M., et al. “Antibody-antigen interactions: contact analysis and binding site topography.”J. Mol. Biol.262:732-745 (1996).
Marshall, J. “Carcinoembryonic antigen-based vaccines.”Semin. Oncol.30(3 Suppl 8):30-36 (2003).
Maynard J., et al. “Antibody Engineering.”Annu. Rev. Biomed. Eng.2:339-376 (2000).
Mendez, M.J., et al. “Functional transplant of megabase human immunoglobulin loci recapitulates human antibody response in mice.”Nat. Genet.2:146-156 (1997).
Morea, V.T.A., et al. “Conformations of the third hypervariable region in the VH domain of immunoglobulins.”J. Mol. Biol.275:269-294 (1998).
Morton, B.A., et al. “Artifactual CEA elevation due to human anti-mouse antibodies.”Arch. Surg.123:1242-1246 (1988).
Neumaier, M., et al. “Cloning of the genes for T84.66, an antibody that has a high specificity and affinity for carcinoembryonic antigen, and expression of chimeric human/mouse T84.66 genes in myeloma and Chinese hamster ovary cells.”Cancer Res.50:2128-2134 (1990).
O'Brien, S., et al. “Humanization of monoclonal antibodies by CDR grafting.”Methods Mol .Biol.207:81-100 (2003).
O'Connor, et al. “Humanization of an antibody against human protein C and calcium- dependence involving framework residues.”Protein Eng.11:321-328 (1998).
Padlan, E.A., et al. “Identification of specificity-determining residues in antibodies.”FASEB J.9:133-139 (1995).
Schroff, R.W., et al. “Human anti-murine responses in patients receiving monoclonal antibody therapy.”Cancer Res.45:879-885 (1985).
Shawler, D.L., et al. “Human immune response to multiple injections of murine monoclonal immunoglobulins.”J. Immunol.135:1530-1535 (1985).
Wagener, C., et al. “Monoclonal antibodies for carcinoembryonic antigen and related antigens as a model system: determination of affinities and specificities of monoclonal antibodies by using biotin-labeled antibodies and avidin as precipitating agent in a solution phase immunoassay.”J. Immunol.130:2302-2307 (1983).
Winter, G., et al. “Making antibodies by phage display technology.”Annu. Rev. Immunol.12:433-455 (1994).
Wong, J.Y.C., “Initial experience evaluating90yttrium-radiolabeled anti-carcinoembryonic antigen chimeric T84.66 in a phase I radioimmunotherapy trial.”Cancer Res.55(23 Suppl):5929s-5934s (1995).
Wong, J.Y.C., et al. “Clinical evaluation of indium-111-labeled chimeric anti-CEA monoclonal antibody.”J. Nucl. Med.38:1951-1959 (1997).
Wong, J.Y.C., et al. “Initial clinical experience evaluating yttrium-90-chimeric T84.66 anticarcinoembryonic antigen antibody and autologous hematopoietic stem cell in patients with carcinoembryonic antigen-producing metastatic breast cancer.”Clin. Cancer Res.5(10 Suppl):3224s-3231s (1999).
Wu, T.T., et al. “An analysis of the sequences of the variable regions of Bence Jones proteins and myeloma light chains and their implications for antibody complementarity.”J. Exp. Med.132:211-250 (1970).
Wu, A.M., et al. “Tumor localization of anti-CEA single-chain Fvs: improved targeting by noncovalent dimers.”Innunotechnology2:221-236 (1996).
Xiang, J., et al. “Framework residues 71 a

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

Humanized anti-CEA T84.66 antibody and uses thereof does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Humanized anti-CEA T84.66 antibody and uses thereof, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Humanized anti-CEA T84.66 antibody and uses thereof will most certainly appreciate the feedback.

Rate now

     

Profile ID: LFUS-PAI-O-3764858

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