Calicheamicin derivative-carrier conjugates

• US 8,153,768 B2
• Filed: 05/02/2003
• Issued: 04/10/2012
• Est. Priority Date: 05/02/2002
• Status: Active Grant

• Current Assignee: Wyeth Holdings Corporation (Pfizer Inc.)
• Original Assignee: Wyeth Holdings Corporation (Pfizer Inc.)
• Inventors: Kunz, Arthur, Moran, Justin Keith, Rubino, Joseph Thomas, Jain, Neera, Vidunas, Eugene Joseph, Simpson, John McLean, Robbins, Paul David, Merchant, Nishith, DiJoseph, John Francis, Ruppen, Mark Edward, Damle, Nitin Krishnaji, Popplewell, Andrew George
• Primary Examiner(s): Reddig, Peter J
• Assistant Examiner(s): Xiao, Yan
• Application Number:
  US10/428,894
• Publication Number:
  US 20040082764A1
• Time in Patent Office: 3,266 Days
• Field of Search: 530/391.1, 530/391.7, 530/387.3, 424/178.1, 424/181.1, 424/1.49
• US Class Current: 530/391.1
• CPC Class Codes: A61K 31/704 attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin digitoxin A61K31/7048
• CPC Class Codes: A61K 47/64 Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent peptidic linkers A61K47/65
• CPC Class Codes: A61K 47/6803 Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
• CPC Class Codes: A61K 47/6809 Antibiotics, e.g. antitumor antibiotics anthracyclins, adriamycin, doxorubicin or daunomycin
• CPC Class Codes: A61K 47/6849 the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/54 F(ab')2
• CPC Class Codes: C07K 2317/55 Fab or Fab'
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/622 Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding

Abstract

Methods for preparing monomeric cytotoxic drug/carrier conjugates with a drug loading significantly higher than in previously reported procedures and with decreased aggregation and low conjugate fraction (LCF) are described. Cytotoxic drug derivative/antibody conjugates, compositions comprising the conjugates and uses of the conjugates are also described. Monomeric calicheamicin derivative/anti-CD22 antibody conjugates, compositions comprising the conjugates and uses of the conjugates are also described.

Claims

1. A composition comprising a drug conjugate, wherein said drug conjugate comprises calicheamicin derivatives and an antibody and has the formula:

2. The composition of claim 1, wherein the antibody comprises a light chain variable region as set forth in SEQ ID NO:

19 and a heavy chain variable region as set forth in SEQ ID NO;

27.

3. The composition of claim 1, wherein the antibody comprises a light chain consisting of residues 21 to 239 of SEQ ID NO:

28 and a heavy chain consisting of residues 20 to 466 of SEQ ID NO;

30, and wherein the antibody is expressed in a mammalian cell.

4. The composition of claim 1, wherein the antibody comprises a light chain consisting of an amino acid sequence resulting from the expression of SEQ ID NO:

29 in a mammalian cell and a heavy chain consisting of an amino acid sequence resulting from the expression of SEQ ID NO;

31 in a mammalian cell.

5. A pharmaceutical composition comprising the composition of claim 1 and a pharmaceutically acceptable excipient, diluent or carrier.