Antitumor protein hybrid and process for the preparation thereof

• US 4,379,145 A
• Filed: 12/15/1980
• Issued: 04/05/1983
• Est. Priority Date: 12/14/1979
• Status: Expired due to Fees

• Current Assignee: Hidematsu Hirai, Teijin Limited
• Original Assignee: Hidematsu Hirai, Teijin Limited
• Inventors: Hara, Takeshi, Masuho, Yasuhiko, Umemoto, Naoji, Hirai, Hidematsu
• Primary Examiner(s): Phillips, Delbert R.
• Application Number:
  US06/216,709
• Time in Patent Office: 841 Days
• Field of Search: 260/112.5 R, 260/112 R, 424/177
• US Class Current: 530/391.9
• CPC Class Codes: A61K 47/6829 Bacterial toxins, e.g. diphteria toxins or Pseudomonas exotoxin A
• CPC Class Codes: A61K 47/6881 Cluster-antibody conjugates, i.e. the modifying agent consists of a plurality of antibodies covalently linked to each other or of different antigen-binding fragments covalently linked to each other
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 16/303 Liver or Pancreas
• CPC Class Codes: C07K 2319/55 containing a fusion with a toxin, e.g. diphteria toxin

Abstract

Antitumor protein hybrid, having a moiety consisting of the antitumor immunoglobulin and a moiety substantially consisting of the fragment A of a diphtheria toxin, which is expressed by the following formula (I):

Ab(NHCO--X--S.sub.1 --S.sub.2 --FA).sub.n                  (I)

(where Ab indicates a moiety consisting of the antitumor immunoglobulin and FA indicates a moiety substantially consisting of the fragment A of a diphtheria toxin; X is an alkylene group or phenylene group which either has or does not have a branching of 1 to 5 carbon atoms. N in the amido bond is a nitrogen atom arising from the amino group in the antitumor immunoglobulin; S₁ and S₂ are both sulfur atoms, S₂ indicating a sulfur atom arising from the disulfide bond in a diphtheria toxin; n stands for an integer of 1 to 5).

This antitumor protein hybrid has remarkable and specific citotoxicity against tumor cells.

Claims

1. Antitumor protein hybrid, having a moiety consisting of the antitumor immunoglobulin and a moiety substantially consisting of the fragment A of a diphtheria toxin, which is expressed by the following formula (I):

space="preserve" listing-type="equation">Ab-(NHCO--X--S.sub.1 --S.sub.2 --FA).sub.n (I)

where Ab indicates a moiety consisting of the antitumor immunoglobulin and FA indicates a moiety substantially consisting of the fragment A of a diphtheria toxin;

X is an alkylene group or phenylene group which either has or does not have a branch chain of 1 to 5 carbon atoms;

N in the amido bond is a nitrogen atom arising from the amino group in the antitumor immunoglobulin;

S₁ and S₂ are both sulfur atoms, S₂ indicating a sulfur atom arising from the disulfide bond in a diphtheria toxin;

n stands for an integer of 1 to 5.

2. Antitumor protein hybrid according to claim 1, wherein X is an ethylene group.

3. Antitumor protein hybrid according to claim 1, wherein FA is a moiety consisting of the fragment A of a diphtheria toxin.

4. A process for the preparation of antitumor protein hybrid expressed by the following formula (I),