US 7,887,805 B2Granted

Recombinant anti-epidermal growth factor receptor antibody compositions

AssigneeSymphogen A/S

InventorsMikkel Wandahl Pedersen, Lucilla Steinaa, Allan Jensen, Klaus Koefoed, Per-Johan Meijer, Robert Carlsson, Charles Pyke, Lars S. Nielsen

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Abstract

The invention relates to the field of recombinant antibodies for use in human cancer therapy. More specifically the invention provides compositions or mixtures of antibodies capable of binding human EGFR. Antibody compositions with 3 or more antibodies showed synergy in reduction of proliferation of representative cancer cell lines. Advantageous results have also been obtained with a composition comprising two different chimeric anti-hEGFR antibodies which show a new mechanism of action based on rapid and efficient receptor internalisation, induction of terminal differentiation and subsequent tumour eradication in an animal model. The antibodies of the invention can be manufactured in one bioreactor as a polyclonal antibody.

An antibody composition comprising at least two distinct anti-EGFR antibodies, wherein at least one of said anti-EGFR antibodies is selected from:

(a) an antibody comprising CDR1, CDR2, and CDR3 of the heavy chain (SEQ ID NO:
40) and CDR1, CDR2, and CDR3 of the light chain (SEQ ID NO:
72) of 992,
(b) an antibody comprising CDR1, CDR2, and CDR3 of the heavy chain (SEQ ID NO:
41) and CDR1, CDR2, and CDR3 of the light chain (SEQ ID NO:
73) of 1024,
(c) an antibody comprising CDR1, CDR2, and CDR3 of the heavy chain (SEQ ID NO:
42) and CDR1, CDR2, and CDR3 of the light chain (SEQ ID NO:
74) of 1030,
(d) an antibody comprising CDR1, CDR2, and CDR3 of the heavy chain (SEQ ID NO:
43) and CDR1, CDR2, and CDR3 of the light chain (SEQ ID NO:
75) of 1042,
(e) an antibody comprising CDR1, CDR2, and CDR3 of the heavy chain (SEQ ID NO:
44) and CDR1, CDR2, and CDR3 of the light chain (SEQ ID NO:
76) of 1208,
(f) an antibody comprising CDR1, CDR2, and CDR3 of the heavy chain (SEQ ID NO:
45) and CDR1, CDR2, and CDR3 of the light chain (SEQ ID NO:
77) of 1229,
(g) an antibody comprising CDR1, CDR2, and CDR3 of the heavy chain (SEQ ID NO:
46) and CDR1, CDR2, and CDR3 of the light chain (SEQ ID NO:
78) of 1254,
(h) an antibody comprising CDR1, CDR2, and CDR3 of the heavy chain (SEQ ID NO:
47) and CDR1, CDR2, and CDR3 of the light chain (SEQ ID NO:
79) of 1257,
(i) an antibody comprising CDR1, CDR2, and CDR3 of the heavy chain (SEQ ID NO:
48) and CDR1, CDR2, and CDR3 of the light chain (SEQ ID NO:
80) of 1260,
(j) an antibody comprising CDR1, CDR2, and CDR3 of the heavy chain (SEQ ID NO:
49) and CDR1, CDR2, and CDR3 of the light chain (SEQ ID NO:
81) of 1261,
(k) an antibody comprising CDR1, CDR2, and CDR3 of the heavy chain (SEQ ID NO:
50) and CDR1, CDR2, and CDR3 of the light chain (SEQ ID NO:
82) of 1277,
(l) an antibody comprising CDR1, CDR2, and CDR3 of the heavy chain (SEQ ID NO:
51) and CDR1, CDR2, and CDR3 of the light chain (SEQ ID NO:
83) of 1284,
(m) an antibody comprising CDR1, CDR2, and CDR3 of the heavy chain (SEQ ID NO:
52) and CDR1, CDR2, and CDR3 of the light chain (SEQ ID NO:
84) of 1308,
(n) an antibody comprising CDR1, CDR2, and CDR3 of the heavy chain (SEQ ID NO:
53) and CDR1, CDR2, and CDR3 of the light chain (SEQ ID NO:
85) of 1320,
(o) an antibody comprising CDR1, CDR2, and CDR3 of the heavy chain (SEQ ID NO:
54) and CDR1, CDR2, and CDR3 of the light chain (SEQ ID NO:
86) of 1344,
(p) an antibody comprising CDR1, CDR2, and CDR3 of the heavy chain (SEQ ID NO:
55) and CDR1, CDR2, and CDR3 of the light chain (SEQ ID NO:
87) of 1347, and
(q) mixtures of two or more of said antibodies in (a)-(p).

46 more elements

Facts

Application

12/074,056Filed 29 Feb 2008 · us provisional application

Priority

DK PA 2007 003171 Mar 2007

Published

US 2009/0004192 A11 Jan 2009

Granted

15 Feb 2011

Term ends

Not estimatedThe source records don’t support an estimate.

Classification13 codes

C07K 16/2863
Against receptors, cell surface antigens or cell surface determinants: against receptors for growth factors, growth regulators
A61K 39/39558
Against materials from animals: against tumor tissues, cells, antigens
A61P 35/00
Antineoplastic agents
A61P 43/00
Drugs for specific purposes, not provided for in groups a61p1/00-a61p41/00

Abstract

Claims53