Stable radioiodine conjugates and methods for their synthesis

• US 6,858,705 B2
• Filed: 10/16/2003
• Issued: 02/22/2005
• Est. Priority Date: 08/28/1996
• Status: Expired due to Fees

• Current Assignee: Immunomedics, Inc.
• Original Assignee: Immunomedics, Inc.
• Inventors: Griffiths, Gary L., Govindan, Serengulam V.
• Primary Examiner(s): Tate, Christopher R.
• Assistant Examiner(s): AUDET, MAURY A
• Application Number:
  US10/686,436
• Publication Number:
  US 20040086454A1
• Time in Patent Office: 495 Days
• Field of Search: 530/345
• US Class Current: 530/345
• CPC Class Codes: A61K 51/0491 Sugars, nucleosides, nucleotides, oligonucleotides, nucleic acids, e.g. DNA, RNA, nucleic acid aptamers
• CPC Class Codes: A61K 51/088 conjugates with carriers being peptides, polyamino acids or proteins antibodies A61K51/10
• CPC Class Codes: A61K 51/10 Antibodies or immunoglobulins; Fragments thereof , the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody
• CPC Class Codes: A61K 51/1093 conjugates with carriers being antibodies
• CPC Class Codes: C07H 3/04 Disaccharides
• CPC Class Codes: C07K 1/1077 by covalent attachment of residues other than amino acids or peptide residues, e.g. sugars, polyols, fatty acids
• CPC Class Codes: G01N 33/543 with an insoluble carrier for immobilising immunochemicals

Abstract

Methods are described for conjugating radioiodinated non-metabolizable peptides to proteins and antibodies with improved yields and qualities of conjugates. Radioiodinated residualizing antibody conjugates comprising any aminopolycarboxylate-appended peptide, or any carbohydrate-appended peptide, are also provided. Additionally, methods are described for conjugating radioiodinated aminopolycarboxylates to proteins and antibodies, as well as for conjugating radioiodinated non-metabolizable carbohydrates to proteins and antibodies by a variety of chemical approaches. The instant radioiodinated residualizing antibody conjugates are particularly stable in vivo and are suitable for radioimmunodetection and radioimmunotherapy.

Claims

1. An aminopolycarboxylate-appended peptide for radioiodinating an antibody selected from the group consisting of:

(ABG)Gly-D-Tyr-D-Lys(ITC-Bz-DTPA)-OH,(ABG-D-Ala-D-Tyr-D-Tyr-D-Lys)-APC, and(ABG-D-Ala-D-Tyr-D-Tyr-D-Lys)₂-APC,

wherein ABG is an antibody binding group, APC is an aminopolycarboxylate, and DTPA is diethylenetriaminepentaacetic acid.

2. The aminopolycarboxylate-appended peptide of claim 1, wherein the antibody binding group is 4-(N-maleimidomethyl)-cyclohexane-1-carbonyl or maleimidomethylcarbonyl.

3. The aminopolycarboxylate-appended peptide of claim 1, wherein said aminopolycarboxylate is NTA (nitrilotriacetic acid), EDTA (ethylenediaminetetraacetic acid), DTPA (diethylenetriaminepentaacetic acid) or TTHA (triethylenetetraminehexaacetic acid).

4. A method for preparing a stable antibody conjugate comprising an aminopolycarboxylate-appended peptide, said method comprising:

(i) radiohalogenating an aminopolycarboxylate-appended peptide according to claim 1 to provide a radiohalogenated aminopolycarboxylate-appended peptide; and

(ii) conjugating said radiohalogenated aminopolycarboxylate-appended peptide to an antibody.