Humanized antibodies that recognize beta amyloid peptide

• US 9,051,363 B2
• Filed: 08/20/2007
• Issued: 06/09/2015
• Est. Priority Date: 12/02/1997
• Status: Expired due to Fees

• Current Assignee: Janssen Sciences Ireland UC (Johnson & Johnson)
• Original Assignee: Janssen Sciences Ireland UC (Johnson & Johnson), Wyeth LLC (Pfizer Inc.)
• Inventors: Basi, Guriq, Saldanha, Jose William, Schenk, Dale B.
• Primary Examiner(s): BALLARD, KIMBERLY
• Application Number:
  US11/842,042
• Publication Number:
  US 20090069544A1
• Time in Patent Office: 2,850 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/53 DNA (RNA) vaccination
• CPC Class Codes: A61K 2039/55505 Inorganic adjuvants
• CPC Class Codes: A61K 2039/55555 Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
• CPC Class Codes: A61K 2039/55566 Emulsions, e.g. Freund's adjuvant, MF59
• CPC Class Codes: A61K 2039/55572 Lipopolysaccharides; Lipid A; Monophosphoryl lipid A
• CPC Class Codes: A61K 2039/55577 Saponins; Quil A; QS21; ISCOMS
• CPC Class Codes: A61K 2039/6037 Bacterial toxins, e.g. diphteria toxoid [DT], tetanus toxoid [TT]
• CPC Class Codes: A61K 2039/605 MHC molecules or ligands thereof
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/739 Lipopolysaccharides
• CPC Class Codes: A61K 38/193 Colony stimulating factors [CSF]
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 39/0007 Nervous system antigens; Prions
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 47/646 the entire peptide or protein drug conjugate elicits an immune response, e.g. conjugate vaccines
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
• CPC Class Codes: A61K 9/2054 : Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/4866 : Organic macromolecular compounds
• CPC Class Codes: A61K 9/7023 : Transdermal patches and similar drug-containing composite devices, e.g. cataplasms galenical aspects of iontophoretic devices A61K9/0009; microneedle arrays A61K9/0021; buccal patches A61K9/006
• CPC Class Codes: A61P 25/00 : Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 : for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: C07K 14/4711 : Alzheimer's disease; Amyloid plaque core protein
• CPC Class Codes: C07K 16/18 : against material from animals or humans
• CPC Class Codes: C07K 2317/24 : containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/34 : Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/565 : Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/567 : Framework region [FR]
• CPC Class Codes: C07K 2317/77 : Internalization into the cell
• CPC Class Codes: C07K 2317/92 : Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: C07K 2319/00 : Fusion polypeptide

Abstract

The invention provides improved agents and methods for treatment of diseases associated with amyloid deposits of Aβ in the brain of a patient. Preferred agents include humanized antibodies.

Claims

1. A method of lessening the severity of Alzheimer'"'"'s disease in the brain of a patient comprising administering a humanized immunoglobulin that binds to Aβ

to a patient having or at risk of the disease thereby lessening the severity of the disease, wherein the humanized antibody comprises;

a humanized immunoglobulin light chain comprising (i) three variable region complementarity determining regions (CDRs) from the 3D6 immunoglobulin light chain,

a humanized immunoglobulin heavy chain comprising (i) three variable region complementarity determining regions (CDRs) from the 3D6 immunoglobulin heavy chain,

wherein 3D6 is an antibody of American Type Culture Collection deposit PTA-5130.

2. The method of claim 1, wherein at least one light or heavy chain variable region framework residue is substituted with the corresponding amino acid residue from the mouse 3D6 light or heavy chain variable region, wherein the framework residue is selected from the group consisting of:

(a) a residue that non-covalently binds antigen directly;

(b) a residue adjacent to a CDR;

(c) a CDR-interacting residue; and

(d) a residue participating in the VL-VH interface.

3. The method of claim 1, wherein the patient has the disease.

4. The method of claim 1, wherein the humanized immunoglobulin is administered intravenously or subcutaneously.

5. A method of reducing plaque burden in the brain of a patient having Alzheimer'"'"'s disease comprising administering a humanized immunoglobulin that binds to Aβ

to the patient thereby reducing plaque burden, wherein the humanized antibody comprises;

a humanized immunoglobulin light chain comprising (i) three variable region complementarity determining regions (CDRs) from the 3D6 immunoglobulin light chain variable region sequence set forth as SEQ ID NO;

2, and (ii) a variable framework region from a human acceptor immunoglobulin light chain sequence, provided that at least one framework residue is substituted with the corresponding amino acid residue from the mouse 3D6 light chain variable region sequence, wherein the framework residue is selected from the group consisting of;

(a) a residue that non-covalently binds antigen directly;

(b) a residue adjacent to a CDR;

(c) a CDR-interacting residue; and

(d) a residue participating in the VL-VH interface; and

a humanized immunoglobulin heavy chain comprising (i) three variable region complementarity determining regions (CDRs) from the 3D6 immunoglobulin heavy chain variable region sequence set forth as SEQ ID NO;

4, and (ii) a variable framework region from a human acceptor immunoglobulin heavy chain, provided that at least one framework residue is substituted with the corresponding amino acid residue from the mouse 3D6 heavy chain variable region sequence, wherein the framework residue is selected from the group consisting of;

(a) a residue that non-covalently binds antigen directly;

(b) a residue adjacent to a CDR;

(c) a CDR-interacting residue; and

(d) a residue participating in the VL-VH interface.

6. The method of claim 5, wherein the humanized immunoglobulin is administered intravenously or subcutaneously.