COMPOSITION AND METHOD FOR THE DIAGNOSIS AND TREATMENT OF DISEASES ASSOCIATED WITH NEURITE DEGENERATION

• US 20150118156A1
• Filed: 12/23/2014
• Published: 04/30/2015
• Est. Priority Date: 01/27/2012
• Status: Active Grant

• Current Assignee: Abbvie Incorporated
• Original Assignee: Abbvie Deutschland GmbH & Company KG (Abbvie Incorporated), Abbvie Incorporated
• Inventors: Mueller, Bernhard, Huang, Lili, Bardwell, Philip D., Kutskova, Yuliya, Memmott, John
• Granted Patent: US 9,365,643 B2
• Time in Patent Office: Days
• US Class Current: 424/1.65
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 49/0002 General or multifunctional contrast agents, e.g. chelated agents
• CPC Class Codes: A61K 49/0058 Antibodies
• CPC Class Codes: A61K 51/1018 against material from animals or humans
• CPC Class Codes: A61K 51/1021 against cytokines, e.g. growth factors, VEGF, TNF, lymphokines or interferons
• 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: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 3/02 Nutrients, e.g. vitamins, minerals
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07B 2200/05 Isotopically modified compounds, e.g. labelled
• CPC Class Codes: C07B 59/008 Peptides; Proteins
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 16/22 against growth factors ; against growth regulators
• CPC Class Codes: C07K 16/28 against receptors, cell surface antigens or cell surface determinants
• 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 2317/31 multispecific
• CPC Class Codes: C07K 2317/33 : Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
• 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 2317/54 : F(ab')2
• CPC Class Codes: C07K 2317/55 : Fab or Fab'
• 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 2317/622 : Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/624 : Disulfide-stabilized antibody (dsFv)
• CPC Class Codes: C07K 2317/76 : Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: G01N 2333/705 : Assays involving receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: G01N 2800/28 : Neurological disorders
• CPC Class Codes: G01N 2800/285 : Demyelinating diseases; Multipel sclerosis
• CPC Class Codes: G01N 33/6896 : Neurological disorders, e.g. Alzheimer's disease

Abstract

Provided herein are antibodies and methods of using the antibodies to treat and diagnose neurite degenerative diseases and disorders.

Claims

1-47. -47. (canceled)

48. An isolated antibody, the antibody comprising:

(a) a variable heavy domain comprising a complementarity-determining region (CDR) 1 comprising an amino acid sequence as set forth in SEQ ID NO;

2, a CDR2 comprising an amino acid sequence as set forth in SEQ ID NO;

3, and a CDR3 comprising an amino acid sequence as set forth in SEQ ID NO;

4, and a variable light domain comprising a CDR1 comprising an amino acid sequence as set forth in SEQ ID NO;

6, a CDR2 comprising an amino acid sequence as set forth in SEQ ID NO;

7, and a CDR3 comprising an amino acid sequence as set forth in SEQ ID NO;

73;

(b) a light chain variable amino acid sequence as set forth in SEQ ID NO;

146 and a heavy chain variable amino acid sequence as set forth in SEQ ID NO;

147, or

(c) a variable heavy domain comprising a complementarity-determining region (CDR) 1 comprising an amino acid sequence as set forth in SEQ ID NO;

2, a CDR2 comprising an amino acid sequence as set forth in SEQ ID NO;

3, and a CDR3 comprising an amino acid sequence as set forth in SEQ ID NO;

4, and a variable light domain comprising a CDR1 comprising an amino acid sequence as set forth in SEQ ID NO;

6, a CDR2 comprising an amino acid sequence as set forth in SEQ ID NO;

7, and a CDR3 comprising an amino acid sequence as set forth in SEQ ID NO;

73, and having the light chain varaiable amino acid sequence as set forth in SEQ ID NO;

146 and the heavy chain variable amino acid sequence as set forth in SEQ ID NO;

147.

wherein the antibody binds to Repulsive Guidance Molecule a (RGMa).

49. The isolated antibody of claim 48, wherein the antibody is selected from the group consisting of a human antibody, an immunoglobulin molecule, a disulfide linked Fv, a monoclonal antibody, an affinity matured, a scFv, a chimeric antibody, a single domain antibody, a CDR-grafted antibody, a diabody, and a humanized antibody, a multispecific antibody, a Fab, a dual specific antibody, a DVD, a Fab′

, a bispecific antibody, a F(ab′

)2, and a Fv.

50. The isolated antibody of claim 49, wherein the antibody is a human antibody.

51. The isolated antibody of claim 49, wherein the antibody is a monoclonal antibody.

52. The isolated antibody of claim 49, wherein the antibody is an affinity matured antibody.

53. The isolated antibody of claim 49, wherein the antibody is a chimeric antibody.

54. The isolated antibody of claim 49, wherein the antibody is a humanized antibody.

55. The isolated antibody of claim 49, wherein the antibody is a Fab, a Fab′

a F(ab′

)₂ or Fv.

56. The isolated antibody of claim 49, wherein the antibody is a dual specific antibody, a DVD or a bispecific antibody.

57. The isolated antibody of claim 48, further comprising a constant sequence of SEQ ID NO:

143.

58. The isolated antibody of claim 48, wherein the antibody comprises a variable heavy domain comprises the CDR1 comprising the amino acid sequence as set forth in SEQ ID NO:

2, the CDR2 comprising the amino acid sequence as set forth in SEQ ID NO;

3, and the CDR3 comprising the amino acid sequence as set forth in SEQ ID NO;

4, and the variable light domain comprises the CDR1 comprising the amino acid sequence as set forth in SEQ ID NO;

6, the CDR2 comprising the amino acid sequence as set forth in SEQ ID NO;

7, and the CDR3 comprising the amino acid sequence as set forth in SEQ ID NO;

73.

59. The isolated antibody of claim 48, wherein the antibody comprises a light chain variable amino acid sequence as set forth in SEQ ID NO:

146 and a heavy chain variable amino acid sequence as set forth in SEQ ID NO;

147.

60. The isolated antibody of claim 48, wherein the antibody comprises a variable heavy domain comprising a complementarity-determining region (CDR) 1 comprising an amino acid sequence as set forth in SEQ ID NO:

2, a CDR2 comprising an amino acid sequence as set forth in SEQ ID NO;

3, and a CDR3 comprising an amino acid sequence as set forth in SEQ ID NO;

4, and a variable light domain comprising a CDR1 comprising an amino acid sequence as set forth in SEQ ID NO;

6, a CDR2 comprising an amino acid sequence as set forth in SEQ ID NO;

7, and a CDR3 comprising an amino acid sequence as set forth in SEQ ID NO;

73, and having the light chain variable amino acid sequence as set forth in SEQ ID NO;

146 and the heavy chain variable amino acid sequence as set forth in SEQ ID NO;

147.

61. A pharmaceutical composition comprising the antibody of claim 48.

62. A pharmaceutical composition comprising the antibody of claim 54.