Tetravalent bispecific receptors, the preparation and use thereof

• US 5,959,083 A
• Filed: 09/21/1994
• Issued: 09/28/1999
• Est. Priority Date: 06/03/1991
• Status: Expired due to Fees

• Current Assignee: Behringwerke Aktiengesellschaft (Sanofi )
• Original Assignee: Behringwerke Aktiengesellschaft (Sanofi )
• Inventors: Bosslet, Klaus, Seemann, Gerhard
• Primary Examiner(s): Eisenschenk, Frank C.
• Application Number:
  US08/308,494
• Time in Patent Office: 1,833 Days
• Field of Search: 530/387.3, 530/388.9, 530/388.3, 530/866, 530/861, 530/389.9, 530/387.1, 530/389.7, 435/70.21, 435/172.2, 435/210 A, 435/253.3, 435/320.1, 435/69.7, 435/188.5, 424/130.1, 424/133.1, 424/134.1, 424/135.1, 424/143.1, 424/155.1, 424/174.1
• US Class Current: 530/387.3
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: C07K 16/30 from tumour cells
• CPC Class Codes: C07K 16/44 against material not provided for elsewhere , e.g. haptens, metals, DNA, RNA, amino acids
• CPC Class Codes: C07K 16/468 Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies
• CPC Class Codes: C07K 2317/31 multispecific
• CPC Class Codes: C07K 2317/50 characterized by immunoglobulin fragments
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C07K 2319/02 containing a signal sequence
• CPC Class Codes: Y10S 530/866 involving immunoglobulin or antibody fragment, e.g. fab', fab, fv, fc, heavy chain or light chain

Abstract

The invention relates to bispecific tetravalent receptors of the formula I ##STR1## or formula II ##STR2## against a tumor-associated antigen and against an agent active against tumors.

Claims

1. A bispecific, tetravalent antibody of FIG. 25 or FIG. 26 wherein H L represents an amino acid sequence comprising one or more hinge regions (H) and a linker peptide (L), thick lines represent peptide bonds, thin lines represent disulfide bridges connecting the two polypeptide chains of said antibody, and wherein the VL1 and VH1 domains of FIGS. 25 and 26 correspond to such domains of a first antibody and are paired naturally, the VL2 and VH2 domains of FIGS. 25 and 26 correspond to such domains of a second, different antibody and are paired naturally, and wherein the CH1 domains are bound to the VH2 domains by 1 to 10 hinge regions H and a suitable linker peptide L.

2. An antibody as claimed in claim 1, wherein the specificity of either the first antibody or the second antibody is directed against animal or human tumor-associated antigen.

3. An antibody as claimed in claim 1, wherein the specificity of either the first antibody or the second antibody has catalytic or enzymatic activity.

4. An antibody as claimed in claim 1, wherein the specificity of either the fast antibody or the second antibody is directed against animal or human tumor-associated antigen and the other antibody has catalytic or enzymatic activity.

5. An antibody as claimed in claim 1, wherein the specificity of either the fist antibody or the second antibody is directed against animal or human tumor-associated antigen and the other antibody specificity is directed against a complexon.

6. An antibody as claimed in claim 1, wherein the variable domains from the first antibody or the second antibody (II) are selected from the group comprising the variable domains of FIGS. 27-34.

7. A pharmaceutical composition comprising an effective amount of an antibody as claimed in claim 1 together with a pharmaceutically acceptable carrier or excipient.

8. A process for the preparation of an antibody as claimed in claim 1, which comprises providing DNA fragments coding for each polypetide chain comprising either VH1, CH1, VH2, CH3, or VL1, CK, or VL2, CH3, or VH1, CH1, VH2, VL2, or VL1, CK, as shown in FIGS. 25 or 26, connecting the appropriate domains by DNA coding for linkers, where appropriate, and expressing the appropriate combination of polypetide chains in a suitable expression system.

9. A bispecific, tetravalent antibody of FIG. 25 wherein H L represents an amino acid sequence comprising one or more hinge regions (H) and a linker peptide (L), thick lines represent peptide bonds, thin lines represent disulfide bridges connecting the two polypeptide chains of said antibody, in which the CH3 domains are replaced by human CH1 domains.