Isolated monoclonal anti-repulsive guidance molecule A antibodies and uses thereof

• US 10,106,602 B2
• Filed: 05/16/2016
• Issued: 10/23/2018
• 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
• Primary Examiner(s): Rooney, Nora M
• Application Number:
  US15/155,815
• Publication Number:
  US 20160326240A1
• Time in Patent Office: 890 Days
• Field of Search: None
• 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 anti-Repulsive Guidance Molecule a (RGMa) antibodies and methods of using the antibodies to treat and diagnose neurite degenerative diseases and disorders.

Claims

1. An isolated monoclonal anti-Repulsive Guidance Molecule a (“

RGMa”

) antibody that comprises a variable heavy chain region comprising a complementarity determining region (CDR) 1 comprising the amino acid sequence of SEQ ID NO;

2, a CDR2 comprising the amino acid sequence of SEQ ID NO;

3, and a CDR3 comprising the amino acid sequence of SEQ ID NO;

4, and a variable light chain region comprising a CDR1 comprising the amino acid sequence of SEQ ID NO;

6, a CDR2 comprising the amino acid sequence of SEQ ID NO;

7, and a CDR3 comprising the amino acid sequence of SEQ ID NO;

8 or of SEQ ID NO;

73.

2. The isolated monoclonal anti-RGMa antibody of claim 1, wherein the CDR3 of the variable light chain region comprises the amino acid sequence of SE ID NO:

73.

3. The isolated monoclonal anti-RGMa antibody of claim 2, wherein the antibody is human.

4. The isolated monoclonal anti-RGMa antibody of claim 2, wherein the antibody comprises a heavy chain immunoglobulin constant domain of an IgG isotype.

5. The isolated monoclonal anti-RGMa antibody of claim 4, wherein the IgG isotype is human IgG1 isotype.

6. The isolated monoclonal anti-RGMa antibody of claim 5, wherein the human IgG1 constant domain is selected from the group consisting of SEQ ID NO:

140, 141, 142 and 143.

7. The isolated monoclonal anti-RGMa antibody of claim 5, wherein the human IgG1 constant domain comprises SEQ ID NO:

143.

8. The isolated monoclonal anti-RGMa antibody of claim 2, wherein the antibody comprises a lambda light chain constant region.

9. The isolated monoclonal anti-RGMa antibody of any one of claims 1 to 8, wherein the antibody comprises a light chain sequence as set forth in SEQ ID NO:

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

147.

10. The isolated monoclonal anti-RGMa antibody of claim 1, wherein the antibody further comprises an agent selected from the group consisting of:

an immunoadhesion molecule, an imaging agent, and a therapeutic agent, wherein the imaging agent is selected from the group consisting of a radiolabel, an enzyme, a fluorescent label, a luminescent label, a bioluminescent label, a magnetic label, and biotin, and wherein the radiolabel is selected from the group consisting of 3H, 14C, 35S, 90Y, 99Tc, 111In, 125I, 131I, 177Lu, 166Ho, and 153Sm.

11. The isolated monoclonal anti-RGMa antibody of claim 2, wherein the antibody binds to the RGMa epitope