Tumor-specific recognition molecules

• US 20060251668A1
• Filed: 12/01/2003
• Published: 11/09/2006
• Est. Priority Date: 11/29/2002
• Status: Active Grant

• Current Assignee: Glycotope Gmbh (Jossa Arznei GmbH)
• Original Assignee: Glycotope Gmbh (Jossa Arznei GmbH)
• Inventors: Danielczyk, Antje, Ravn, Peter, Christensen, Peter Astrup, Goletz, Steffen, Karsten, Uwe, Stahn, Renate
• Granted Patent: US 8,088,357 B2
• Time in Patent Office: Days
• US Class Current: 424/185.100
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 47/6851 the antibody targeting a determinant of a tumour cell
• CPC Class Codes: A61K 47/6903 the form being semi-solid, e.g. an ointment, a gel, a hydrogel or a solidifying gel
• CPC Class Codes: A61K 51/1045 against animal or human tumor cells or tumor cell determinants
• CPC Class Codes: C07K 16/3076 against structure-related tumour-associated moieties
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/622 Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/626 Diabody or triabody
• CPC Class Codes: C07K 2319/00 Fusion polypeptide

Abstract

The invention relates to recognition molecules which are directed towards tumors and can be used in the diagnosis and therapy of tumor diseases.

Claims

1-73. -73. (canceled)

74. A recognition molecule comprising an amino acid sequence which contains

(i) the amino acid sequence SEQ ID NO. 1 and

(ii) the amino acid sequence SEQ ID NO. 2 or 3 and

(iii) the amino acid sequence SEQ ID NO. 4, 5 or 6,

and specifically binds the core 1 antigen.

75. The recognition molecule according to claim 74, further comprising an amino acid sequence which contains

(i) the amino acid sequence SEQ ID NO. 7 or 8 or 9 and

(ii) the amino acid sequence SEQ ID NO. 10 or 11 and

(iii) the amino acid sequence SEQ ID NO. 12 or 13,

and specifically binds the core 1 antigen.

76. The recognition molecule according to claim 74, wherein the antibody framework sequences

a) FRH1, FRH2, FRH3 and FRH4 for the variable heavy chain VH are the following amino acid sequences,

the amino acid position corresponding to the numbering according to Kabat:

for FRH1 inposition 

1Q or E 

2V 

3Q, K or T 

4L 

5K or V 

6E or Q 

7S 

8G 

9A10E11L or V1.2V or K13R or K14P15G16T or A17S18V19K20I or V21S or P22C23K24A, V, S or T25S26G27Y, F, S or D28T29F, L or I30Tfor FRH2 in position36W37V38K or R39Q40R or A41P42G43H or Q44G45L46E47W or R48I or M49Gfor FRH3 in position66K or R67A or V68T69L or M70T71A, L or T72D73T74S75S or T76S77T78A79Y80M81Q or E82L 

82aS 

82bS or R 

82cL83T or R84S85E86D87S or T88A89V90Y91F or y92C93A94Y, K or Rfor FRH4 in position103 

W104 

G105 

Q106 

G107 

T108 

T, S or L109 

V or L110 

T111 

V112 

S113 

S or A

b) FRL1, FRL2, FRL3 and FRL4 for the variable light chain VT, are the following amino acid sequences, the amino acid position corresponding to the numbering according to Kabat;

for FRL1 in position 

1D 

2I, V or L 

3Q or L 

4M 

5T 

6Q 

7T or S 

8P 

9L10S11L12P13V14S or T15L or P16G17D or E18Q or P19A20S21I22S23Cfor FRL2 in position35W36Y37L38Q39K40P41G42Q43S44P45K or Q46L47L 



4BI or V49Yfor FRL3 in position57G58V59P60D61R62F63S64G65S66G67S68G69T70D71F72T73L74K75I76S77R78V79E80A81E82D83L or V84G85V86Y87Y88Cfor FRL4 in position98F99G100 

G or Q101 

G102 

T103 

K104 

L105 

E106 

I or L106aK107 

R108 

A.

77. The recognition molecule according to claim 74, wherein the recognition molecule comprises a combination of sequences SEQ ID Nos. 46 and 80, or SEQ ID Nos. 47 and 81, or SEQ ID Nos. 48 and 80, or SEQ ID Nos. 50 and 80, or SEQ ID Nos. 53 and 82, or SEQ ID Nos. 52 and 83, or SEQ ID Nos. 55 and 83, or SEQ ID Nos. 54 and 80, or SEQ ID Nos. 51 and 83, or SEQ ID Nos. 49 and 80, or SEQ ID Nos. 56 and 90, or SEQ ID Nos. 57 and 90, or SEQ ID Nos. 57 and 86, or SEQ ID Nos. 58 and 87, or SEQ ID Nos. 56 and 91, or SEQ ID Nos. 59 and 91, or SEQ ID Nos. 60 and 87, or SEQ ID Nos. 61 and 90, or SEQ ID Nos. 56 and 88, or SEQ ID Nos. 56 and 85, or SEQ ID Nos. 59 and 90, or SEQ ID Nos. 62 and 90, or SEQ ID Nos. 59 and 86, or SEQ ID Nos. 74 and 92, or SEQ ID Nos. 63 and 87, or SEQ ID Nos. 74 and 87, or SEQ ID Nos. 74 and 89, or SEQ ID Nos. 74 and 85, or SEQ ID Nos. 64 and 86, SEQ ID Nos. 74 and 86, or SEQ ID Nos. 63 and 86, or SEQ ID Nos. 65 and 85, or SEQ ID Nos. 65 and 86, or SEQ ID Nos. 66 and 85, or SEQ ID Nos. 67 and 87, or SEQ ID Nos. 68 and 86, or SEQ ID Nos. 72 and 88, or SEQ ID Nos. 69 and 90, or SEQ ID Nos. 70 and 90, or SEQ ID Nos. 69 and 92, or SEQ ID Nos. 73 and 86, or SEQ ID Nos. 69 and 89, or SEQ ID Nos. 71 and 92, or SEQ ID Nos. 56 and 86, or SEQ ID Nos. 65 and 92.

78. The recognition molecule according to claim 74, wherein said recognition molecule is a single-chain antibody fragment, a multibody, a Fab fragment, a fusion protein of an antibody fragment with peptides or proteins and/or an immunoglobulin of the IgG, IgM, IgA, IgE, IgD isotypes and/or subclasses thereof.

79. A construct comprising the recognition molecules according to claim 74, wherein the recognition molecules are fused, chemically coupled, covalently or non-covalently associated with (i) immunoglobulin domains of various species, (ii) enzyme molecules, (iii) inter-action. domains, (iv) domains for stabilization, (v) signal sequences, (vi) fluorescent dyes, (vii) toxins, (viii) catalytic antibodies, (ix) one or more antibodies or antibody fragments with different specificity, (x) cytolytic components, (xi) immunomodulators, (xii) immunoeffectors, (xiii) MHC class I or class II antigens, (xiv) chelating agents for radioactive labelling, (xv) radioisotopes, (xvi) liposomes, (xvii) transmembrane domains, (xviii) viruses and/or (xix) cells.

81. Use of a recognition molecule according to claim 74 in the prophylaxis, prevention, diagnosis, reduction, therapy, follow-up and/or aftercare of tumor diseases and/or metastases.

82. The use according to claim 81, wherein the recognition molecule is a non-labelled recognition molecule, which corresponds to an IgM or IgG or has been derived therefrom.

83. The use according to claim 81, wherein the recognition molecules are multibodies.

84. Use of a construct according to claim 79 in the prophylaxis, prevention, diagnosis, reduction, therapy, follow-up and/or aftercare of tumor diseases and/or metastases.