Humanized antibodies that bind to the antigen bound by antibody NR-LU-13

• US 6,358,710 B1
• Filed: 06/09/1997
• Issued: 03/19/2002
• Est. Priority Date: 06/07/1996
• Status: Expired due to Fees

• Current Assignee: Poniard Pharmaceuticals, Inc.
• Original Assignee: NeoRx Corporation
• Inventors: Mallett, Robert W., Rees, Anthony R., Graves, Scott S., Searle, Stephen M. J., Hylarides, Mark D., Reno, John M., Pedersen, Jan T., Henry, Andrew H.
• Primary Examiner(s): Ungar, Susan
• Assistant Examiner(s): DAVIS, MINH TAM B
• Application Number:
  US08/871,488
• Time in Patent Office: 1,744 Days
• Field of Search: 424/130.1, 424/133.1, 424/134.1, 424/138.1, 424/139.1, 424/141.1, 424/142.1, 424/174.1, 435/4, 435/325, 435/358, 435/330, 435/70.1, 436/547, 530/387.1, 530/387.3
• US Class Current: 435/70.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• 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: A61K 47/68 the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
• CPC Class Codes: A61K 47/6898 using avidin- or biotin-conjugated antibodies
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: C07K 1/1133 by redox-reactions involving cystein/cystin side chains
• CPC Class Codes: C07K 16/00 Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies antibodies with enzymatic activity, e.g. abzymes C12N9/0002
• CPC Class Codes: C07K 16/30 from tumour cells
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/41 Glycosylation, sialylation, or fucosylation
• CPC Class Codes: C07K 2317/732 Antibody-dependent cellular cytotoxicity [ADCC]
• CPC Class Codes: C07K 2317/734 Complement-dependent cytotoxicity [CDC]
• CPC Class Codes: C07K 2319/00 Fusion polypeptide

Abstract

Humanized antibodies which bind the NR-LU-13 antigen, conjugates containing such antibodies, and their use in pretargeting methods and conventional antibody therapy and immunodiagnosis are provided.

Claims

1. The humanized antibody NRX 451 or an antigen-binding fragment thereof, wherein the murine parent antibody has ATCC Accession No:

CRL-12360, and wherein the light chain variable region thereof comprises SEQ ID NO;

18 and the heavy chain variable region thereof comprises SEQ ID NO;

19.

2. The antibody or antibody fragment of claim 1 wherein said antibody or said antibody fragment either does not possess N-linked glycosylation or its N-linked glycosylation has been modified post expression to reduce immunogenicity or toxicity, and wherein said antibody or antibody fragment specifically binds to the antigen bound by antibody NR-LU-13(ATCC ACCESSION NO:

CRL-12360).

3. The antibody or antibody fragment of claim 2 wherein the N-linked glycosylation has been modified chemically.

4. The antibody or antibody fragment of claim 3 wherein the N-linked glycosylation has been modified by oxidation followed by stabilization of the aldehydes generated by oxidation.

5. The antibody or antibody fragment of claim 4 wherein the N-linked glycosylation has been modified by oxidation followed by reduction.

6. The antibody or antibody fragment of any one of claims 1-5 wherein the polynucleotides encoding said antibody or said antibody fragment have been substituted or deleted in the glycosylation motif Asn-Xaa-Ser(Thr) of the C_H2 domain to prevent N-linked glycosylation in the C_H2 domain, wherein Xaa is any amino acid and Ser and Thr are interchangeable.

7. A composition comprising an antibody or antibody fragment according to claim 6 in combination with a pharmaceutically acceptable carrier or diluent.