Transgenic animals for producing specific isotypes of human...

Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives

Reexamination Certificate

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C536S023100, C435S320100, C800S013000, C800S018000

Reexamination Certificate

active

07049426

ABSTRACT:
The present invention provides fully human antibodies in a transgenic animal of a desired isotype in response to immunization with any virtually any desired antigen. The human immunoglobulin heavy chain transgene in the foregoing animals comprises a human constant region gene segment comprising exons encoding the desired heavy chain isotype, operably linked to switch segments from a constant region of a different heavy chain isotype, i.e., a non-cognate switch region. Said additional constant region segment comprises a switch region and human constant region coding segment, wherein the constant region coding segment is operably linked to a switch region that it is not normally associated with, i.e., a non-cognate switch region. In the transgenes of the invention, the non-cognate switch region may be a switch region from a different species than the constant region coding segment. The switch region and membrane exons of the invention may comprise a human gamma-2 constant region and the secreted constant region exons are from a human gamma-1 or a human gamma-4 constant region.

REFERENCES:
patent: 5569825 (1996-10-01), Lonberg et al.
patent: 5625126 (1997-04-01), Lonberg et al.
patent: 5877397 (1999-03-01), Lonberg et al.
patent: WO 94/02602 (1994-02-01), None
patent: WO 98/24884 (1998-06-01), None
patent: WO 98/24893 (1998-06-01), None
Pluschke et al. (1998) J. Immunol. Meth., vol. 215, 27-37.
Zou et al. (1994) Curr. Biol., vol. 4, 1099-1103.
L. Green et al., “Regulation of B Cell Development by Variable Gene Complexity in Mice Reconstituted with Human Immunoglobulin Yeast Artificial Chromosomes,”J. Exp. Med., 188:483-495 (1998).
M.R. Mowatt et al., “DNA Sequence of the Murine γ1 Switch Segment Reveals Novel Structural Elements,”J. Immunology, 136:2674-2683 (1986).
Y.-R. Zou et al., “Cre-loxP Mediated Gene Replacement: a Mouse Strain Producing Humanized Antibodies,”Current Biol., 4:1099-1103 (1994).
V. Arulampalam et al., “Elevated Expression Levels of an Ig Transgene in Mice Links the IgH 3′ Enhancer to the Regulation of IgH Expression,”International Immunology, 8:1149-1157 (1996).
V. Arulampalam et al., “The Enhancer Shift: A Model to Explain the Developmental Control of IgH Gene Expression in B-lineage Cells,”Immunology Today, 18:549-554 (1997).
F.D. Batista et al., “Affinity Dependence of the B Cell Response to Antigen: A Threshold, a Ceiling, and the Importance of Off-Rate,”Immunity, 8:751-759 (1998).
A.G. Betz et al., “Discriminating Intrinsic and Antigen-selected Mutational hotspots in Immunoglobulin V Genes,”Immunology Today, 14:405-409 (1993).
A.G. Betz et al., “Elements Regulating Somatic Hypermutation of an Immunoglobulin κ Gene: Critical Role for the Intron Enhancer/Matrix Attachment Region,”Cell, 77:239-248 (1994).
C.I. Bindon et al., “Human Monoclonal IgG Isotypes Differ in Complement Activating Function at the Level of C4 As Well AS C1q,”J. Exp. Med., 168:127-142 (1988).
S. Biocca et al., “Expression and Targeting of Intracellular Antibodies in Mammalian Cells,”The EMBO Journal, 9:101-108 (1990).
J.B. Bolen, “Protein Tyrosine Kinases in the Initiation of Antigen Receptor Signaling,”Current Opinion in Immunology, 7:306-311 (1995).
A. Bottaro et al., “S Region Transcriptionper sePromotes Basal IgE Class Switch Recombination But Additional Factors Regulate the Efficiency of the Process,”The EMBO Journal, 13:665-674 (1994).
M. Brüggemann et al., “Comparison of the Effector Functions of Human Immunoglobulins Using a Matched Set of Chimeric Antibodies,”J.Exp. Med.166:1351-1361 (1987).
M. Brüggemann, “Evolution of the Rat Immunoglobulin Gamma Heavy-chain Gene Family,”Gene, 74:473-482 (1988).
M. Brüggemann et al., “Human Antibody Production in Transgenic Mice: Expression from 100 kb of the Human IgH Locus,”Eur. J. Immunol., 21:1323-1326 (1991).
M. Brüggemann et al., “Sequence of a Rat Immunoglobulin γ2cHeavy Chain Constant Region cDNA: Extensive Homology to Mouse γ3′”Eur. J. Immunol., 18:317-319 (1988).
M. Brüggemann et al., “Production of Human Antibody Repertoires in Transgenic Mice,”Current Opinion in Biotechnology, 8:455-458 (1997).
M. Brüggemann et al., “Construction, Function and Immunogenicity of Recombinant Monoclonal Antibodies,”Behring, Inst. Mitt., 87:21-24 (1990).
M. Brüggemann et al., “Strategies for Expressing Human Antibody Repertoires in Transgenic Mice,”Immunology Today, 17:391-397 (1996).
M. Brüggemann et al., “Designer Mice: The Production of Human Antibody Repertoires in Transgenic Animals,”Generation of Antibodies by Cell and Gene Immortalization, 7:33-40 (1993).
Brüggemann et al., “The Immunogenicity of Chimeric Antibodies,”J. Exp. Med., 170:2153-2157 (1989).
M. Brüggemann et al., “A Repertoire of Monoclonal Antibodies with Human Heavy Chains from Transgenic Mice,”Proc. Natl. Acad. Sci. USA, 86:6709-6713 (1989).
M. Brüggemann et al., “Novel Antibodies by DNA Manipulation”,Monoclonal Antibody Therapy, 45:91-105 (1988).
C. Bützler et al., “Rapid Induction of B-cell Lymphomas in Mice Carrying a Human IgH/c-mycYAC,”Oncogene, 14:1383-1388 (1997).
A. Cattaneo et al., “Polymeric Immunoglobulin M is Secreted by Transfectants of Non-lymphoid Cells in the Absence of Immunoglobulin J Chain”,EMBO Jour., 6:2753-2758 (1987).
J. Chen et al., “Mutations of the Intronic IgH Enhancer and its Flanking Sequences Differentially Affect Accessibility of the JHLocus,”The EMBO Journal, 12:4635-4645 (1993).
T.K. Choi et al., “Transgenic Mice Containing a Human Heavy Chain Immunoglobulin Gene Fragment Cloned in a Yeast Artificial Chromosome,”Nature Genetics, 4:117-123 (1993).
M. Cogné et al., “A Class Switch Control Region at the 3′ End of the Immunoglobulin Heavy Chain Locus,”Cell, 77: 737-747 (1994).
G.P. Cook et al., “Regulated Activity of the IgH Intron Enhancer (Eμ) in the T Lymphocyte Lineage,”International Immunology, 7:89-95 (1995).
P. Dariavach et al., “The Mouse IgH 3′ -Enhancer,”Eur. J. Immunol., 21:1499-1504 (1991).
N.P. Davies et al., “Extension of Yeast Artificial Chromosomes by Cosmid Multimers,”Nucleic Acids Research, 21:767-768 (1993).
N.P. Davies et al., “Creation of Mice Expressing Human Antibody Light Chains by Introduction of a Yeast Artificial Chromosome Containing the Core Region of the Human Immunoglobulin κ Locus,”Bio/Technology, 11:911-914 (1993).
N.P. Davies et al., “Targeted Alterations in Yeast Artificial Chromosomes for Inter-species Gene Transfer,”Nucleic Acids Research, 20:2693-2698 (1992).
A.L. DeFranco, “The Complexity of Signaling Pathways Activated by the BCR,”Current Opinion in Immunology, 9:296-308 (1997).
S. Delphin et al., “Characterization of an Interleukin 4 (IL-4) Responsive Region in the Immunoglobulin Heavy Chain Germline ε Promoter: Regulation by NF-IL-4, a C/EBP Family Member and NF-κB/p50,”J. Exp. Med., 181:181-192 (1995).
J. Durdik et al.., “Isotype Switching by a Microinjected μ Immunoglobulin Heavy Chain Gene in Transgenic Mice”,Proc. Natl. Acad. Sci. USA, 86:2346-2350 (1989).
M. R. Ehrenstein et al., “Targeted Gene Disruption Reveals a Role for Natural Secretory IgM in the Maturation of the Primary Immune Response,”Proc. Natl. Acad. Sci. USA, 95:10089-10093 (1998).
J. Ellison et al. “Linkage and Sequence Homology of Two Human Immunoglobulin γ Heavy Chain Constant Region Genes,”Proc. Natl. Acad. Sci. USA, 79:1984-1988 (1982).
J. Ellison et al., “Nucleotide Sequence of a Human Immunoglobulin Cγ4Gene,”DNA, 1: 11-18 (1981).
J.W. Ellison

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