Method for making humanized antibodies

• US 6,639,055 B1
• Filed: 11/02/2000
• Issued: 10/28/2003
• Est. Priority Date: 06/14/1991
• Status: Expired due to Fees

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: Presta, Leonard G., Carter, Paul J.
• Primary Examiner(s): HELMS, LARRY RONALD
• Application Number:
  US09/705,686
• Time in Patent Office: 1,090 Days
• Field of Search: 530/387.1, 530/387.3, 530/388.1, 435/69.6, 435/69.7, 424/133.1
• US Class Current: 530/387.3
• 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: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 16/28 against receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: C07K 16/2809 against the T-cell receptor (TcR)-CD3 complex
• CPC Class Codes: C07K 16/32 against translation products of oncogenes
• CPC Class Codes: C07K 16/465 with additional modified FR-residues
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/31 multispecific
• CPC Class Codes: C07K 2317/54 F(ab')2
• CPC Class Codes: C07K 2317/55 Fab or Fab'
• CPC Class Codes: C07K 2317/732 Antibody-dependent cellular cytotoxicity [ADCC]
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: G06F 15/00 Digital computers in general details G06F1/00 – G06F13/00; Data processing equipment in general

Abstract

Variant immunoglobulins, particularly humanized antibody polypeptides are provided, along with methods for their preparation and use. Consensus immunoglobulin sequences and structural models are also provided.

Claims

1. A humanized antibody variable domain comprising non-human CDR amino acid residues which bind an antigen incorporated into a human antibody variable domain, and further comprising a Framework Region (FR) amino acid substitution at a site selected from the group consisting of:

4L, 35L, 38L, 43L, 44L, 46L, 58L, 62L, 64L, 65L, 66L, 67L, 68L, 69L, 73L, 85L, 98L, 2H, 4H, 36H, 39H, 43H, 45H, 69H, 70H, 74H, 75H, 76H, 78H, and 92H, utilizing the numbering system set forth in Kabat.

2. The humanized antibody variable domain of claim 1, wherein the substituted residue is the residue found at the corresponding location of the non-human antibody from which the non-human CDR amino acid residues are obtained.

3. The humanized antibody variable domain of claim 1, wherein no human FR residue other than those set forth in the group has been substituted.