Tris-maleimido compounds as intermediates in trifunctional antibody synthesis

• US 5,091,542 A
• Filed: 03/09/1990
• Issued: 02/25/1992
• Est. Priority Date: 03/09/1990
• Status: Expired due to Fees

• Current Assignee: Hybritech, Inc. (Danaher Corporation)
• Original Assignee: Hybritech, Inc. (Danaher Corporation)
• Inventors: Ahlem, Clarence, Huang, Ann E.
• Primary Examiner(s): Ivy, C. Warren
• Assistant Examiner(s): Chang, Celia
• Application Number:
  US07/491,386
• Time in Patent Office: 718 Days
• Field of Search: 548/521, 435/7.1
• US Class Current: 548/521
• 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: C07D 207/452 with hydrocarbon radicals, substituted by hetero atoms, directly attached to the ring nitrogen atom
• CPC Class Codes: C07K 1/10 using coupling agents C07K1/006 takes precedence
• CPC Class Codes: C07K 16/468 Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies

Abstract

The present invention is directed to a compound for use as an intermediate in the production of novel trifunctional antibody-like compounds. More particularly, the present invention is directed to a compound of the formula: ##STR1## wherein X is ##STR2## wherein k=1 or 0;

wherein Z is ##STR3## wherein s=1 or 0;

wherein n=1 or 0;

wherein q=1 or 0;

wherein Y is ##STR4## wherein Y'"'"', is ##STR5## wherein p or m may be the same or different and are integers ranging from 0 to 20 with the proviso that when n=0, the sum of m and p is an integer ranging from 1 to 20, whereas when n=1, p and m are each an integer that is at least 1 and the sum of p and m is an integer ranging from 2 to 20;

wherein R¹ is straight or branched chain lower alkyl having from 1 to 6 carbon atoms or lower alkoxy having from 1-6 carbon atoms; and

wherein R² is hydrogen, phenyl, --COOH, or straight or branched chain lower alkyl having from 1-6 carbon atoms, with the proviso that the lower alkyl moiety may be mono substituted by --NH₂, --OH, or --COOH.

The compound of the present invention is useful as a trivalent coupling agent for linking Fab'"'"'-like fragments to form both bifunctional and trifunctional antibody-like compounds.

Claims

1. A compound of the formula:

##STR22## wherein X is ##STR23## wherein k=1 or 0;

wherein Z is ##STR24## wherein s=1 or 0;

wherein n=1;

wherein q=1 or 0;

wherein Y is ##STR25## wherein Y'"'"' is ##STR26## wherein p or m may be the same or different and are integers ranging from 0 to 20 with the provisos that when n=1, p and m are each an integer that is at least 1 and the sum of p and m is an integer ranging from 2 to 20;

wherein R¹ is straight or branched chain lower alkyl having from 1 to 6 carbon atoms or lower alkoxy having from 1-6 carbon atoms; and

wherein R² is hydrogen phenyl, --COOH, or straight or branched chain lower alkyl having from 1-6 carbon atoms optionally monosubstituted by --NH₂, --OH, or --COOH.

2. The compound according to claim 1 wherein Y is ##STR27##

3. The compound according to claim 2 which is:

##STR28##

4. The compound according to claim 2 which is:

##STR29##

5. A compound according to claim 1 which is:

##STR30##

6. The compound according to claim 1 which is:

##STR31##

7. The compound according to claim 1 wherein n=1, s=0, and m and p are each an integer that is at least 1 and the sum of m and p is an integer from 2 to about 20.

9. The compound according to claim 1 which is:

##STR33##

11. The compound according to claim 1 which is:

##STR35##

8. The compound having the formula:

##STR32##

10. The compound having the formula:

##STR34##