(12) United States Patent (10) Patent No.: US 9,708.635 B2 Murphy Et Al

(12) United States Patent (10) Patent No.: US 9,708.635 B2 Murphy Et Al

USOO9708635B2 (12) United States Patent (10) Patent No.: US 9,708.635 B2 Murphy et al. (45) Date of Patent: *Jul.18, 2017 (54) METHODS OF MAKING ANUCLEC ACID 15/907 (2013.01); A0IK 2207/15 (2013.01); ENCOOING A HUMAN VARIABLE REGION A0IK 2217/05 (2013.01); A0IK 2227/105 (2013.01); A0IK 2267/01 (2013.01); C07K (71) Applicant: Regeneron Pharmaceuticals, Inc., 2317/10 (2013.01); C07K 2317/21 (2013.01); Tarrytown, NY (US) C07K 2317/24 (2013.01); C07K 2317/51 (72) Inventors: Andrew J. Murphy, (2013.01); C07K 2317/515 (2013.01); C07K Croton-On-Hudson, NY (US); George 2317/56 (2013.01); C12N 2800/204 (2013.01) D. Yancopoulos, Yorktown Heights, NY (58) Field of Classification Search (US); Margaret Karow, Santa Rosa CPC ............ A01K 67/0278: A01K 67/0275: A01 K Valley, CA (US); Lynn Macdonald, 2227/105: A01K 2267/01: A01K 2207/15; White Plains, NY (US): Sean Stevens, A01K 2227/10; C07K 16/00; C07K San Diego, CA (US); Aris N. 16/462; C12N 15/85; C12N 15/907; Economides, Tarrytown, NY (US); C12N 15/902; C12N 2800/30; A61 K David M. Valenzuela, Yorktown 49/OO Heights, NY (US) See application file for complete search history. (73) Assignee: Regeneron Pharmaceuticals, Inc., Tarrytown, NY (US) (56) References Cited (*) Notice: Subject to any disclaimer, the term of this U.S. PATENT DOCUMENTS patent is extended or adjusted under 35 5,202,238 A 4/1993 Fell, Jr. et al. U.S.C. 154(b) by 0 days. 5,436,149 A 7/1995 Barnes This patent is Subject to a terminal dis 5,545,807 A * 8/1996 Surani et al. ..................... 800/6 claimer. 5,614,396 A 3/1997 Bradley et al. 5,625,126 A * 4/1997 Lonberg et al. ................ 800, 18 5,770.429 A 6/1998 Lonberg et al. (21) Appl. No.: 13/719,819 5,789,215 A 8, 1998 Berns et al. (22) Filed: Dec. 19, 2012 (Continued) FOREIGN PATENT DOCUMENTS (65) Prior Publication Data EP 438 474 A1 7, 1991 US 2013/0210137 A1 Aug. 15, 2013 EP 1204 740 B1 5, 2002 Related U.S. Application Data (Continued) (60) Continuation of application No. 13/154,976, filed on OTHER PUBLICATIONS Jun. 7, 2011, which is a continuation of application No. 1 1/595,427, filed on Nov. 9, 2006, which is a Clark et al (Nature Reviews: Genetics. 2003, 825-833.* continuation of application No. 10/624,044, filed on (Continued) Jul. 21, 2003, now abandoned, which is a division of application No. 09/784,859, filed on Feb. 16, 2001, now Pat. No. 6,596,541, which is a Primary Examiner — Anoop Singh continuation-in-part of application No. 09/732,234, (74) Attorney, Agent, or Firm — Brendan T. Jones; Neil filed on Dec. 7, 2000, now Pat. No. 6,856,251. Miyamoto; Foley Hoag LLP (60) Provisional application No. 60/244,665, filed on Oct. 31, 2000. (57) ABSTRACT (51) Int. C. A method for engineering and utilizing large DNA vectors to AIK 67/027 (2006.01) target, via homologous recombination, and modify, in any C07K 6/00 (2006.01) desirable fashion, endogenous genes and chromosomal loci C07K I6/46 (2006.01) in eukaryotic cells. These large DNA targeting vectors for CI2N 15/90 (2006.01) eukaryotic cells, termed LTVECs, are derived from frag CI2P 2L/00 (2006.01) ments of cloned genomic DNA larger than those typically CI2N 15/67 (2006.01) used by other approaches intended to perform homologous CI2N 15/85 (2006.01) targeting in eukaryotic cells. Also provided is a rapid and C07K 6/28 (2006.01) convenient method of detecting eukaryotic cells in which the (52) U.S. C. LTVEC has correctly targeted and modified the desired CPC .......... CI2P21/00 (2013.01); A0IK 67/0275 endogenous gene(s) or chromosomal locus (loci) as well as (2013.01); A0IK 67/0278 (2013.01); C07K the use of these cells to generate organisms bearing the 16/00 (2013.01); C07K 16/28 (2013.01); C07K genetic modification. I6/462 (2013.01): CI2N 15/67 (2013.01); CI2N 15/85 (2013.01); C12N 15/8509 (2013.01); C12N 15/902 (2013.01); CI2N 10 Claims, 7 Drawing Sheets US 9,708.635 B2 Page 2 (56) References Cited WO WO-2014/071397 A2 5, 2014 WO WO-2015,088643 A1 6, 2015 U.S. PATENT DOCUMENTS WO WO-2016,081923 A2 5, 2016 5,877,397 A 3, 1999 Lonberg et al. 5,928,914 A 7, 1999 E. et al. OTHER PUBLICATIONS 3.252 A ge. Shepati et al. Niemann et al (Rev. Sci, Tech. Off. Int. Spiz. 2005, (24), 285-298.* 6,069,010 A 5, 2000 Choi Ristevski et al Molecular Biotechnology, 2005, 153-163.* 6,075,181 A 6/2000 Kucherlapati et al. Gama Sosa et al (Brain Struct Funct, 2010, 214:91-109.* 6,096,878 A 8/2000 Honjo et al. Smith Journal of Biotechnology 99 (2002) 1-22.* 6,114,598 A 9/2000 Kucherlapati ..... AOK 67/0275 Qi et al Hypertension. 2005, 45:1004-1011.* 435/325 Parng, The Journal of Immunology, 1996, 157: 5478-5486.* ... f 1939 agist al. Kaushik, Veterinary Immunology and irnmunopathology 87 (2002) 6,528,313 B1 3/2003 Le Mouellic et al. 347-350.* 6,570,061 B1 5/2003 Rajewsky et al. Wagner et al Abstract Nucleic Acids Res. 1994; 22(8): 1389-93.* 6,586,251 B2 7/2003 Economides et al. Butler Rev Scientifique et Technique Office International Des 6,596,541 B2 7/2003 Murphy et al. Epizooties. 1998, 17, 1, 43-70.* 6,638,768 B1 10/2003 Le Mouellic et al. Sen and Baltimore Cell, 1986, 46, 705-716).* 6,653,113 B1 11/2003 Berns et al. Hochepied et al Stem Cells, 2004, 22:441-447.* 3. R. 39 chari et al. Schoonjans et al Stem Cells, 2003, 21:90-97. 6998.54 B2 2/2006 Bruggemann Anna B. Auerbach, Acta Biochimica Polonica, 2004, 51 :9-31. 7,105.348 B2 9/2006 Murphy et al. Pera Journal of Cell Science 113:5-10, 2000.* 7,129,084 B2 10/2006 Buelow et al. Sen and Baltimore, Cell, 1986, 705-716.* 7,145,056 B2 12/2006 Jakobovits et al. Taki et al Science, 1993: 262, 5137. 1268- 127I.* 7,435,871 B2 10/2008 Green et al. Cox et al Trends in Biotechnology vol. 19 No. 7 Jul. 2001, 7,501,552 B2 3, 2009 Lonberg et al. 247-25O.* 2329, R: $38, tions al. Pawlitzsky et al The Journal of Immunology, 2006, 176: 6839 9.012,717 B2 4/2015 Macdonald et al. 6851.* 2002/0028488 A1 3/2002 Singh et al. Johnston et al The Journal of Immunology, 2006, 176: 4221-4234.* 2002/0178456 A1 11, 2002 Buellow Ebert et al (Immunity, 2011, 25; 34(2): 175-87.* 2003/0182675 A1 9, 2003 Etches et al. Hewitt et al Nature Immunology, 2008, 9(4), 396-404.* 2004/0018626 A1 1/2004 Murphy et al. NCBI accession No. AF477986. 1, Feb. 2012, pp. 1-2.* 2004/O158880 A1 8, 2004 Buelow et al. Retter et al The Journal of Immunology, 2007, 179: 2419-2427.* 2005.0054055 Al 3, 2005 Kucherlapati et al. Sheng et al. Nucleic Acid Research, 1995, 23, 1990-1996.* 2005. O144655 A1 6/2005 Economides et al. Zhang, et al., Nat Genet, 20:123-8, 1998.* 2005/O153392 A1 7/2005 Buelow et al. ck 2006/0015957 A1* 1/2006 Lonberg et al. ................ 800s Hill et al. Genomics, 64:111-3, 2000. 2006, OO26696 A1 2/2006 Buelow et al. Sen and Baltimore, Cell, 1986, see p. 705-716.* 2006, OO26703 A1 2/2006 Lonberg et al. Taki et al (Science, 1993: 262, 5137. 1268-127I.* 2006,0040363 A1 2/2006 Kucherlapati et al. Pawlitzsky et al (The Journal of Immunology, 2006, 176: 6839 2007/0280945 A1 12, 2007 Stevens et al. 6851.* 2011/0258710 Al 10/2011 Murphy et al. MacDonald et al., PNAS, 2010, 111, 5147-5152.* 2013, O137101 A1 5/2013 Economides et al. Angrand, P.O. et al., “Simplified Generation of Targeting Constructs 2013/0254911 A1 9, 2013 Macdonald et al. Using ET Recombination.” Nucleic Acids Res. 27(17): e16 (1999). 2014/0178879 A1 6, 2014 Economides et al. Cheng, S. et al., “Long PCR.” Nature 369(6482):684-685 (1994). Deng, C. et al., “Reexamination of Gene Targeting Frequency as a FOREIGN PATENT DOCUMENTS Function of the Extent of Homology Between the Targeting Vector and the Target Focus.” Mol. Cell. Biol. 12(8):3365-3371 (1992). 536; 33. Durdik, J. et al., “Isotype Switching by a Microinjected mu Immu WO WO-90,04036 A1 4f1990 noglobulin Heavy Chain Gene in Transgenic Mice,” Proc. Natl. WO WO-91/00906 A1 1, 1991 Acad. Sci. USA 86(7):2346-2350 (1989). WO WO-93,04169 A1 3, 1993 Fishwild, D.M. et al., “High-Avidity Human IgGkappa Monoclonal WO WO-94f02602 A1 2, 1994 Antibodies From a Novel Strain of Minilocus Transgenic Mice.” WO WO-94,04667 A1 3, 1994 Nat. Biotechnol. 14(7):845-851 (1996). WO WO-94/25585 A1 11, 1994 Foord, O.S. et al., “Long-Distance PCR." PCR Methods Appl. WO WO-96,30498 A1 10, 1996 3(6): S149-S161 (1994) WO WO-98.24893 A2 6, 1998 WO WO-99/45962 A1 9, 1999 Forozan, F. et al., “Genome Screening by Comparative Genomic WO WO-01/19394 A2 3, 2001 Hybridization.” Trends Genet. 13(10:405-409 (1997). WO WO-02/12437 A2 2, 2002 Gerstein, R.M.

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