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`EXHIBIT A
`
`

`

`(12) United States Patent
`Cabilly et al.
`
`US006331415B1
`US 6,331,415 B1
`Dec. 18, 2001
`
`(10) Patent N0.:
`(45) Date of Patent:
`
`(54) METHODS OF PRODUCING
`IMMUNOGLOBULINS, VECTORS AND
`TRANSFORMED HOST CELLS FOR USE
`THEREIN
`
`(75) Inventors: Shmuel Cabilly, Monrovia; Herbert L.
`Heyneker, Burlingame; William E.
`Holmes, Paci?ca; Arthur D. Riggs, La
`Verne; Ronald B. Wetzel, San
`Francisco, all of CA (US)
`
`(73) Assignee: Genentech, Inc., South San Francisco,
`CA (Us)
`
`( * ) Notice:
`
`Subject to any disclaimer, the term of this
`patent is extended or adjusted under 35
`U.S.C. 154(b) by 0 days.
`
`(21) Appl. No.: 07/205,419
`(22) Filed:
`Jun. 10, 1988
`
`Related US. Application Data
`
`(63) Continuation of application No. 06/483,457, ?led on Apr. 8,
`1983, now Pat. No. 4,816,567.
`
`(51) Int. C1.7 ......................... .. C12N 15/13; C12N 15/00;
`C12N 15/63
`
`(52) us. Cl. ..................... .. 435/69.6; 435/69.1; 435/697;
`435/701; 435/7021; 435/71.1; 435/712;
`435/320; 435/2521; 435/252.3; 435/252.33;
`435/254.11; 435/2542; 435/254.21; 435/455;
`435/471; 435/483; 435/485
`
`(58) Field of Search ................................ .. 435/691, 69.7,
`435/711, 70.1, 71.2, 320, 261, 252.1, 252.3,
`81, 55, 56, 69.6, 252.33, 254.21, 483
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`Primary Examiner—Phillip Gambel
`(74) Attorney, Agent, or Firm—Burns, Doane, SWecker &
`Mathis, LLP
`(57)
`
`ABSTRACT
`
`The invention relates to processes for producing an immu
`noglobulin or an immunologically functional immunoglo
`bulin fragment containing at least the variable domains of
`the immunoglobulin heavy and light chains. The processes
`can use one or more vectors Which produce both the heavy
`and light chains or fragments thereof in a single cell. The
`invention also relates to the vectors used to produce the
`immunoglobulin or fragment, and to cells transformed With
`the vectors.
`
`36 Claims, 19 Drawing Sheets
`
`

`

`US 6,331,415 B1
`Page 2
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