Patent ID: 6315997
Filing Date: 2001-11-13
Classification: A61K,C07K,G01N

Abstract:
A method of reducing tumor growth or reducing the size of a tumor, comprising administering to a subject in need of treatment an amount of a modified antibody which selectively binds the human milk fat globule (HMFG) antigen, and competes as well or better with the unmodified antibody for binding the HFMG, wherein the modified antibody comprises a non-HMFG antigen-binding peptide from a first species, and an HMFG antigen-binding peptide comprising the light and heavy chains of the variable region of an antibody of a second species, wherein at least one chain of the non-HMFG antigen-binding peptide is linked to the HMFG antigen-binding peptide, the chains may be linked to one another at a site other than the antigenic binding site, and at least one chain of the HMFG antigen-binding peptide has 1 to 46 amino acids subsituted with at least one amino acid selected from the group consisting of the following amino acids at the specific sites and chains:Light Chain Heavy Chain Position Amino Acid Substitution Amino Acid Substitution 1 D PVLKARGHDE or Q 2 WKCRHV or I M or V 3 V or L LQR or K 4 MPTQLV or I M or L 5 T VD or E 6 Q QD or E 7 TIAD or S T or S 8 PA or E G or E 9 LF or P G 10 T or S DA or G 11 NL or V VF or L 12 S or P I or V 13 V KE or Q 14 S or T P 15 PFI or L G 16 G RSE or G 17 TEQ or D PA or S 18 PS or Q M 19 V or A R or K 20 S V or L 21 I S 22 S C 23 C TSE or A 24 V or A 25 S 26 G 27 F 28 AINS or T 29 F 30 S 35 W 36 IVHNYF or L W 37 WLVKRTHDE or Q WIFLVMATG or Q 38 Q R 39 R or K Q 40 FLKARTGQP or S VA or S 41 G PLVARTSHNE or Q 42 Q G or E 43 P or S K 44 P SR or G 45 or K L 46 RV or L Q or E 47 WILMTSN or V W 48 FPLVMTS or I STG or V 49 Y or S A 57 WVTSGDNE or Q 58 IYFLVMAT or Q 59 S or P 60 N or D 61 T or R 62 F 63 IYPLKARSG or T 64 D or G 65 S 66 G R 67 A or S F 68 VMCARSGQD or E IS or T 69 T I 70 D L or S 71 F R 72 T VKRTSGHDE or N 73 L N or D 74 NLRE or K FPLVTGDNA or S 75 L or I EN or K 76 IT or S NTRK or S 77 S or R TNIVSM or R 78 ALI or V LA or V 79 KGQ or E FH or Y 80 P or A L 81 ILVKMAGDN or E E or Q 82 D M 82a SDN or I 82b IR or S 82c PLVMAG or E 83 MV or L EKT or R 84 LVARTS or G SPVTI or A 85 IM or V WIYFPLMCRGD or E 86 Y D 87 IMSHEFY or L M or T 88 C A or G 89 ITVM or L 90 HF or Y 91 Y 92 C 93 ASHAV or T 94 TSDQLAWR or G 98 F 99 G 100 IPVKRTGAS or Q 101 G 102 T 103 IYMATGHDEQNR or K A or W 104 LG or V YH or G 105 ILVTSGHNE or Q THR or Q 106 YLVKMRTD or I G 106a PLVTI 107 IVLMATSGNER or K AQ or T 108 STGM or L 109 IKLT or V 110 SL or T 111 V 112 T or S and 113 PLVATG or S, or single chain thereof;and following the modified antibody to bind to any antigen present on a neoplastic cell present in the tumor to form antibody-cell antigen complexes, wherein the modified antibody is operatively linked to a therapeutic agent.