Transgenic non-human animals capable of producing heterologous a

Details Transgenic non-human animals capable of producing heterologous a Transgenic non-human animals capable of producing heterologous a

1997-02-14

1999-02-23

Chambers, Jasemine C.

Chemistry: molecular biology and microbiology

Vector, per se

4351723, 935 34, 536 2353, C12N 1500, C12N 1579, C12N 1511

Patent

active

058742999

ABSTRACT:
The invention relates to transgenic non-human animals capable of producing heterologous antibodies, i.e., antibodies encoded by immunoglobulin heavy and light chain genes not normally found in the genome of that species of non-human animal. In one aspect of the invention, transgenes encoding unrearranged heterologous human immunoglobulin heavy and light chains are introduced into a non-human animal thereby forming a transgenic animal capable of producing antibodies encoded by human immunoglobulin genes. Such heterologous human antibodies are produced in B-cells which are thereafter immortalized, e.g., by fusing with an immortalizing cell line such as a myeloma or by manipulating such B-cells by other techniques to perpetuate a cell line capable of producing a monoclonal heterologous antibody. The invention also relates to heavy and light chain immunoglobulin transgenes for making such transgenic non-human animals as well as methods and vectors for disrupting endogenous immunoglobulin loci in the transgenic animal. The invention also includes methods to generate a synthetic immunoglobulin variable region gene segment repertoire used in transgene construction and methods to induce heterologous antibody production using animals containing heterologous rearranged or unrearranged heavy and light chain immunoglobulin transgenes.

REFERENCES:
patent: 5545807 (1996-08-01), Surani
Alt et al., TIG--Aug. 1985.
Berman et al., EMBO J. 7:727 (1988).
Berton et. al., Proc. Natl. Acad. Sci. USA 86:2829 (1989).
Bollag et al., Annu. Rev. Genet. 23:199 (1989).
Bruggemann et al., Eur. J. Immunol. 21:1323 (1991).
Bruggemann et al., Proc. Natl. Acad. Sci. USA 86:6709 (1989).
Bucchini et al., Nature 326:409 (1987).
Buttin, TIG 3(8) (1987).
Capecchi, TIG 5:70 (1989).
Capecchi, Science 244:1288 (1989).
Coffman et. al., J. Immunol. 136:949 (1986).
Coffman et al., J. Immunol. 139:3685 (1987).
Doetschman et al., Nature 330:576 (1987).
Durdik et al., Proc. Natl. Acad. Sci. USA 86:2346 (1989).
Esser and Radbruch, EMBO J. 8:483 (1989).
Ferrier et al., EMBO J. 9:117 (1990).
Forni, Eur. J. Immunol. 20:983 (1990).
Gerstein et al., Cell 63:537 (1990).
Goodhardt et al., Proc. Natl. Acad. Sci. USA 84:4229 (1987).
Gordon, The Mount Sinai Journal of Medicine 53:223 (1986).
Hagman et al., J. Exp. Med. 169:1911 (1989).
Hofker et al., Proc. Natl. Acad. Sci. USA 86:5567 (1989).
Humphries et al., Nature 331:446 (1988).
Ichihard et al., EMBO J. 7:4141 (1988).
Iglesias et al., Nature 330:482 (1987).
Jaenisch, Science 240:1468 (1988).
James and Bell, J. of Immunol. Methods 100:5 (1987).
Jasin and Berg, Genes & Development 2:1353 (1988).
Kenny et al., J. of Immunol. 142:4466 (1989).
Kitamura et al., Nature 350:423 (1991).
Koller et al., Proc. Natl. Acad. Sci. USA 86:8932 (1989).
Lin et al., Proc. Natl. Acad. Sci. USA 82:1391 (1985).
Linton et al., Cell 59:1049 (1989).
Lo et al., Eur. J. Immunol. 21:1001 (1991).
Lorenz et al., Nucl. Acids Res. 15:9667 (1987).
Lutzker and Alt, Mol. Cell Biol. 8:1849 (1988).
Mansour et al., Nature 336:348 (1988).
Miller et al., Nature 295:428 (1982).
Mills et.al., Nucl. Acids. Res. 18:7305 (1991).
Mills et al., Nature 306:809 (1983).
Mowatt et. al., J.Immunol. 136:2674 (1986).
Muller et al., Eur. J. Immunol. 19:923 (1989).
Murray & Szostak, Nature 305:189 (1983).
Neuberger et al., Nature 338:350 (1989).
Nikaido et al., J. Biol. Chem. 257:7322 (1982).
Nikaido et al., Nature 292:845 (1981).
Nussenzweig et al., J. Exp. Med. 167:1969 (1988).
Oettinger et al., Science 248:1517 (1990).
Petters, Vet. Immunol. Immunopath. 17:267 (1987).
Pettersson et al., Nature 344:165 (1990).
Rabbits et. al., Nucl. Acids Res. 9:4509 (1981).
Rath et al., J. of Immunol. 146:2841 (1991).
Rath et al., J. of Immunol. 143:2074 (1989).
Ravetch et al., Proc. Natl. Acad. Sci. USA 77:6734 (1980).
Reid et al., Proc. Natl. Acad. Sci. USA 86:840 (1989).
Ritchie et al., Nature 312:517 (1984).
Rothman et al., Intl. Immunol. 2:621 (1990).
Rusconi et al., Nature 314:330 (1985).
Sato et al., Biochem. Biophys. Res. Comm. 154:264 (1988).
Scanos and Bieberich, Advances in Genetics 24:285 (1987).
Sevidy and Sharp, Proc. Natl. Acad. Sci. USA 86:227 (1989).
Shimizu et al., Proc. Natl. Acad. Sci. USA 86:8020 (1989).
Shimizu et al., J. Exp. Med. 173:1385 (1991).
Sideras et. al., Intl. Immunol. 1:631 (1989).
Siebenlist et al., Nature 294:631 (1981).
Smithies et al., Nature 317:230 (1985).
Snapper et. al., Science 236:944 (1987).
Song et al., Proc. Natl. Acad. Sci. USA 84:6820 (1987).
Soriano et al., Cell 64:693 (1991).
Stavnezer et al., Proc. Natl. Acad Sci. USA 85:7704 (1988).
Stites et al., in Basic and Clinical Immunology, p. 50 (1984).
Storb, In Immunoglobulin Genes, pp. 303-326 (Academic Press, Limited), 1989.
Storb et al., Immunological Reviews 89:85 (1986).
Szurek et al., J. Immunol. 135:620 (1985).
Tahara et al., Immunogenetics 32:351 (1990).
Tanaka et al., J. Exp. Med. 175:597 (1992).
Taussig et al., Immunology Today 10:143 (1989).
Thomas and Capecchi, Cell 51:503 (1987).
Thomas et al., Cell 44:419 (1986).
Uhlmann and Peyman, Chemical Reviews 90:544 (1990).
Vlasov et al., Chemical Abstracts, p. 28, 112:229433X (1990).
Weaver et al., Cell 42:117 (1985).
Yamamura et al., Proc. Natl. Acad. Sci. USA 83:2152 (1986).
Yancopoulos and Alt, Ann. Rev. Immunol. 4:339 (1986).
Yancopoulos and Alt, Cell 40:271 (1985).
Yasui et al., Eur. J. Immunol. 19:1399 (1989).
Zijustra et al., Nature 342:435 (1989).
Zimmer and Gruss, Nature 338:150 (1989).

Affiliated with

Also associated with

Rating

Transgenic non-human animals capable of producing heterologous a does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Transgenic non-human animals capable of producing heterologous a, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Transgenic non-human animals capable of producing heterologous a will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-306145