Antibodies to receptor of advanced glycation end products (RAGE) and uses thereof

• US 8,323,651 B2
• Filed: 05/08/2009
• Issued: 12/04/2012
• Est. Priority Date: 05/09/2008
• Status: Active Grant

• Current Assignee: Abbvie Deutschland GmbH & Company KG (Abbvie Incorporated)
• Original Assignee: Abbott GmbH & Company KG (Abbott Laboratories Incorporated), Abbott Laboratories Incorporated
• Inventors: Hsieh, Chung-Ming, DiGiammarino, Enrico L., Fox, Gerard B., Harlan, John E., Schmidt, Martin, Mueller, Reinhold, Ebert, Ulrich, Gu, Jijie, Wu, Zhen, Luo, Feng, Loebbert, Ralf, Nimmrich, Volker
• Primary Examiner(s): Emch, Gregory S
• Application Number:
  US12/437,715
• Publication Number:
  US 20100028359A1
• Time in Patent Office: 1,306 Days
• Field of Search: None
• US Class Current: 424/143.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/02 Muscle relaxants, e.g. for tetanus or cramps
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/24 Antidepressants
• 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: A61P 27/06 Antiglaucoma agents or miotics
• 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 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: C07K 16/28 against receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily
• CPC Class Codes: C07K 16/464 Igs containing CDR-residues from one specie grafted between FR-residues from another
• CPC Class Codes: C07K 2317/14 Specific host cells or culture conditions, e.g. components, pH or temperature
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 : Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/567 : Framework region [FR]
• CPC Class Codes: C07K 2317/76 : Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/92 : Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: C12P 21/005 : Glycopeptides, glycoproteins
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present application relates to isolated proteins, particularly monoclonal antibodies, in particular CDR-grafted, humanized antibodies which bind to RAGE protein. Specifically, these antibodies have the ability to inhibit the binding of RAGE to its various ligands. The antibodies or portions thereof of described in the present application are useful for treating a disease or disorder characterized by or induced by pathophysiological ligands of RAGE, for example misfolded proteins like amyloid β and advanced glycation-end-products.

Claims

1. An isolated antibody or antigen-binding fragment thereof comprising an antigen binding domain, said antibody or antigen-binding fragment capable of binding an epitope of a human RAGE molecule, said antigen binding domain comprising 3 heavy chain variable region CDRs having the sequences SEQ ID NO:

10, SEQ ID NO;

11, and SEQ ID NO;

12, and 3 light chain variable region CDRs having the sequences SEQ ID NO;

14, SEQ ID NO;

15, and SEQ ID NO;

16.

2. The antibody according to claim 1, further comprising a human acceptor framework.

3. The antibody according to claim 2, wherein said antibody comprises at least one framework mutation selected from the group consisting of:

(a) the heavy chain sequence positions of 1, 2, 68, 70, 72, 76, 85, 89, 95;

(b) the light chain sequence positions of 11, 13, 43, 49, 58, 70, 87; and

(c) combinations thereof.

4. The antibody of claim 3, wherein said antibody comprises at least one framework mutated variable domain having an amino acid sequence selected from the group consisting of:

(a) the heavy chain sequences of SEQ ID NO;

62, 67, 68 and 69;

(b) the light chain sequences of SEQ ID NO;

63, 64, 65 and 66; and

(c) combinations thereof.

5. The antibody of claim 1 comprising at least one heavy chain variable domain selected from SEQ ID NO:

9, 56 and 57; and

/or at least one light chain variable domain selected from SEQ ID NO;

13, 58 and 59.

6. A pharmaceutical composition comprising the antibody of claim 1, and a pharmaceutically acceptable carrier.

7. A composition for the sustained or controlled release of an antibody said composition comprising

(a) a formulation, wherein said formulation comprises the antibody of claim 3 in crystallized form as an ingredient;

and

(b) at least one polymeric carrier.

8. An isolated nucleic acid molecule, which encodes the amino acid sequence of the antibody or antigen-binding fragment of claim 1.

9. A vector, which comprises the isolated nucleic acid molecule of claim 8.

10. An isolated host cell, which comprises the vector of claim 9.

11. A method of producing an antibody capable of binding RAGE or an antigen binding fragment thereof, comprising culturing the host cell of claim 10 in culture medium under conditions sufficient to produce the antibody or antigen binding fragment thereof.

12. An antibody or antigen binding fragment thereof produced according to the method of 11.