Therapeutic compounds comprised of anti-Fc receptor antibodies

57 Pages·2013·2.87 MB·English

US006395272B1
United States Patent
(12) (10) Patent N0.: US 6,395,272 B1
De0 et al. (45) Date of Patent: *May 28, 2002
(54) THERAPEUTIC COMPOUNDS COMPRISED FOREIGN PATENT DOCUMENTS
0F ANTI-PC RECEPTOR ANTIBODIES W0 WO 91/00360 1/1991 ......... .. C12P/21/00
_ _ W0 W0 91 05871 5/1991
(75) Inventors. Yashwant M: De0,~Audubon, PA (US), W0 WO 91/03493 3/1992 ~~~~~~~~~ “ C07K/15/28
J 0e] Goldsteln, EdlSOIl; Robert W0 W0 92 05793 4/1992
Gralian°> Frenchtowm both of NJ W0 WO 94/10332 5/1994 ......... .. C12P/21/08
(US); Chellan Somasundaram, W0 W0 95/09917 4/1995 ......... .. C12N/15/13
Allentown’ PA (Us) OTHER PUBLICATIONS
(73) Assignee: MedereX, Inc., Princeton, NJ (US) Chen, J. et al. (1995) “An Immunoconjugate of
Lys3—Bombesin and Monoclonal Antibody 22 Can Speci?
( * ) Notice: Subject to any disclaimer, the term of this Cally Induced FcgammaRI (CD64)—Dependent
patent is eXIended or adjusted under 35 Monocyte— and Neutrophil—Mediated Lysis of Small Cell
U-S-C- 154(1)) by 0 days- Carcinoma of the Lung Cells” Clinical Cancer Research, 1
(4); 425434.
This patent 15 Subject I0 a terminal (115- Fanger, M. et al. (1994) “Production and Use Of Anti—FcR
Claimef- Bispeci?c Antibodies” Immunomethods 4(1): 72—81.
Fridman, W.H. (1991), “Fc receptors and immunoglobulin
(21) Appl, No; 09/102,716 binding factors”, The FASEB Journal, vol. 5:2684—2690.
_ GraZiano, R. et al. (1995) “Construction and Characteriza
(22) Flled: Jun‘ 22’ 1998 tion of a HumaniZed Anti—Gamma—Ig Receptor Type I
_ _ (Fcgamma RI) Monoclonal Antibody” Th eJ ournal ofImmu
Related US. Application Data nology, 155 (10): 49965002
. . . . . JaWetZ et al. (1991) Medical Microbiology 19th Edition.
60 DlVlSlOIl of a lication No. 08/661,052, ?led on Jun. 7, ’ “ ’
( ) 1996, now PHEPNO. 5,837,243, which is a continuation-in- Jung’ Gundram’ et_ a1" (1991)’ Target c_en_lnduced T Cell
part of application No, 08/484,172, ?led on ]un_ 77 1995_ Activation With B1— and Tr1spec1?c Antibody Fragments”,
Eur J. Immunol vol. 21 pp. 2431—2435.
(51) Int. Cl. 7 ..................... .. A61K 39/395,. C12P 21/08,, Mabondzo, A' et7 a1' (19974 ) “AntibodYADePendent Cellular
C07K 16/00’ C07K 16/46’ C07K 18/00 CytotoXicity and Neutralization of Human Immunode?
(52) US. Cl. .............................. .. 424/1381; 424/1311; Ciency Virus Type 1 By High Affinity CrOSS_Linking of gp41
424/1351; 424/1361; 424/1411; 424/1421; to Human Macrophage Fc IgG Receptor Using Bispeci?c
424/1431; 424/1551; 424/1561; 530/3873; Antibody” Journal of General Virology, 75 (6):1451—1456.
530/387.7; 530/388.1; 530/388.2; 530/388.22; Repp, R' et a1' (1994) “G_CSF Stimulated Neutroph?s AS
_ 530/388'7; 530/388'8; 530/388'85 Effector Cells In Immunotherapy With A Bispeci?c Anti
(58) Field of Search ......................... .. 424/1381, 131.1, body to FCgammaRI and To HER_2/neu (MDX210); Pre
424/1351, 1361, 1411, 1421, 143-1, 155-1, clinical Studies”, Immunobiology, 191 (2—3): 250—251.
156-1 Fanger et al. (1992), “Bespeci?c Antibodies” Critical
Reviews in Immunology 12(3,4):101—124.
(56) References Cited
Primary Examiner—Geetha P. Bansal
U.S. PATENT DOCUMENTS (74) Attorney, Agent, or Firm—Lahive & Cock?eld, LLP;
Jane E. Remillard; Peter W. Dini
4,753,894 A 6/1988 Frankel et al. ............ .. 436/548
4,943,533 A 7/1990 Mendelsohn et al. .. 435/240.27 (57) ABSTRACT
4,954,617 A 9/1990 Fanger et al. ............. .. 530/387
5,084,396 A 1/1992 Morgan, Jr. et al. . 436/513 Multispeci?c multivalent molecules Which are speci?c to an
5,288,477 A 2/1994 Bacus ......................... .. 424/2 Fc receptor (FcR), and therapeutic uses and therapeutic uses
5,558,864 A 9/1996 Bendig et al. 424/1331 and methods for making the molecules are described.
5,597,569 A 1/1997 Siegall et al. 424/1831
5,635,600 A 6/1997 Fanger et al. .......... .. 530/387.3 6 Claims, 29 Drawing Sheets

U.S. Patent May 28,2002 Sheet 3 0f 29 US 6,395,272 B1
800 —
—0——f/ - /
600_ 22 [U
400 —
Z00 -
0| 1 YIIIIIII I IIIIIII‘
/ /
Ab CONT/{MANN (#g/m/I
FIG.5

U.S. Patent May 28,2002 Sheet 5 0f 29 US 6,395,272 B1
TV////////////////////////////////////
WWWT\\\\m\\\\\\
T70/U%/////////// / ///// /%
LAWmw u
//////////,// /V/V\/
V////////////////////%
E.Q$GQQQEQEGEQICQw
/// ///
5 44/ '
lyg/m/
. pg/m/ . g/m/
Alli/B00)’
FIG. 8
33w3N3E%Q%S Q
‘l
0 /0 /00

U.S. Patent
May 28, 2002 Sheet 7 0f 29 US 6,395,272 B1
‘ | I III!!!‘ I
‘l /
Ab CMCt'I/MAT/Ul/ Lug/ml}
FIG. 12
#22
FIG.13.