US006686163B2 (12) United States Patent (10) Patent No.: US 6,686,163 B2 Allen et al. (45) Date of Patent: Feb. 3, 2004 (54) CODING SEQUENCE HAPLOTYPE OF THE 5,912,127 A 6/1999 Narod et al. ................... 435/6 HUMAN BRCA1 GENE 5.948,643 A 9/1999 Rubinfeld et al. ......... 435/69.1 5,965,377 A 10/1999 Adams et al. ............. 435/7.23 (75) Inventors: Antonette C. P. Allen, Severn, MD 6,033,857 A 3/2000 Tavtigian et al. .............. 435/6 (US); Tracy S. Angelly, Gaithersburg, 6,045,997 A 4/2000 Futreal et al. - - - - - - - - - - 435/6 MD (US); Tammy Lawrence, Laurel, 6,051,379 A 4/2000 Lescallett et al. .............. 435/6 6,083,698 A 7/2000 Olson et al. ................... 435/6 MD (US); Sheri J.Olson, Falls 6,124,104 A 9/2000 Tavtigian et al. ............ 435/7.2 Church, VA (US); Mark B. Rabin, 6,130,322 A * 10/2000 Murphy et al. ................ 435/6 Rockville, MD (US) FOREIGN PATENT DOCUMENTS (73) Assignee: Gene Logic Inc., Gaithersburg, MD EP O705902 A1 4/1996 (US) EP O705903 A1 4/1996 EP O699.754 A1 6/1996 (*) Notice: Subject to any disclaimer, the term of this GB 2307477 A 5/1997 patent is extended or adjusted under 35 WO WO9304200 3/1993 U.S.C. 154(b) by 0 days. WO WO9519369 7/1995 WO WO9722689 6/1997 WO WO973O108 8/1997 (21) Appl. No.: 10/022,819 WO WO9815654 4/1998 (22) Filed: Dec. 20, 2001 OTHER PUBLICATIONS (65) Prior Publication Data Abeliovich et al. (1997) The Founder Mutations 185deAG US 2003/0027166 A1 Feb. 6, 2003 and 5382insCin BRCA and 6174delTin BRACA2 Appear in 60% of Ovarian Cancer and 30% of Early-Onset Breast Related U.S. Application Data Cancer Patients among Ashkenazi Women. Am. J. Hum. Genetics 60(3): 505–514. (62) Division of application No. 09/074,452, filed on May 6, Couch et al. (1996) Mutations and Polymorphisms in the 1998, now abandoned. Familial Early-Onset Breast Cancer (BRCA1) Gene. Human Mutation 8(1):8-18. (51) Int. Cl. ........................... C12Q 1/68; C07H21/04 Dunning et al. (1997) Common BRCA1 variants and sus (52) U.S. Cl. ....................... 435/6; 435/320.1; 435/69.1; ceptibility to breast and Ovarian cancer in the general 435/325; 536/23.1; 536/24.3; 536/24.32; population. Human Molecular Genetics 6(2):285-289. 536/23.5; 530/350 Durrocher et al. (1996) Comparison of BRCA1 polymor (58) Field of Search ............................... 536/23.1, 24.3, phisms, rare Sequence variants and/or missense mutations in 536/23.2, 23.5; 435/320.1, 6,325, 69.1; unaffected and breast/ovarian cancer populations. Human 514/44; 530/350, 300 Molecular Genetics 5(6): 835-842. Friedman et al. (1994) Confirmation of BRCA1 by analysis (56) References Cited of germline mutations linked to breast and ovarian cancer in Funari et al. (1997) Growth suppression of glioma cells by 4,458,066 A 7/1984 Caruthers et al. ............. 536/27 PTEN requires functional phosphatase catalytic domain. 4,683.202 A 7/1987 Mullis ......................... 435/91 Processings of the National Academy of Sciences (USA) 4,704,362 A 11/1987 Itakura et al. ... 435/253 94(23): 12479-12484. 5,221,619 A 6/1993 Itakura et al. ... 435/69.4 5,445,934 A 8/1995 Fodor et al. ................... 435/6 (List continued on next page.) 5,510,270 A 4/1996 Fodor et al. ... ... 436/518 5,545,531. A 8/1996 Rava et al. .... 435/6 Primary Examiner-Kenneth R. Horlick 5,547,839 A 8/1996 Dower et al. .................. 435/6 Assistant Examiner-Cynthia Wilder 5,561,058 A 10/1996 Gelfand et al. ... ... 435/912 (74) Attorney, Agent, or Firm-Morgan Lewis & Bockius 5,582,989 A 12/1996 Caskey et al. ................. 435/6 LLP 5,583,013 A 12/1996 Itakura et al. ... 435/69.4 5,589,330 A 12/1996 Shuber ............. ... 435/6 (57) ABSTRACT 5,593,840 A 1/1997 Bhatnagar et al. ... ... 435/6 - 0 5,624,803 A 4/1997 Noonberg et al. ... ... 435/6 The invention is directed to isolated coding sequences and to 5,633,134. A 5/1997 Shuber ................ 435/6 the protein Sequences they code for. The coding Sequence for 5,650,316 A 7/1997 Aggarwal et al. .......... 435/375 BRCA1(omi4) gene is provided together with the protein 5,654,155 A * 8/1997 Murphy et al. ................ 435/6 Sequence it codes for. The BRCA1(omi4) sequence is used 5,693.473 A 12/1997 Shattuck-Eidens et al. .... 435/6 for identifying an individual having an increased genetic 5,709.999 A 1/1998 Shattuck-Eidens et al. .... 435/6 Susceptibility to breast or ovarian cancer because the patient 5,710,001 A 1/1998 Skolnich et al................ 435/6 has an inherited causative mutation in their BRCA1 gene. 5,726,019 A 3/1998 Sidransky .................. 435/6 This invention is also related to a method of performing gene 5,750,4005,747.282 A * 5/1998 MurphySkolnick et et al. al. ........................... 435/69.1 ass, therapyh withith the isolateisolated BRCA1(om14) i4) codingdi sequence 5,753,441 A 5/1998 Skolnicket al. ... ... 435/6 and protein replacement therapy with the BRCA1(omi4) 5,756.294 A 5/1998 White et al. ...... ... 435/6 protein. 5,858,669 A 1/1999 Levine ......... ... 435/6 5,891.857 A 4/1999 Holt et al. .................... 514/44 25 Claims, No Drawings US 6,686,163 B2 Page 2 OTHER PUBLICATIONS Jensen et al., “Characterization of Baculovirus-Expressed Hacia et al. 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