Methods of treating retinal nerve fiber layer degeneration with monoclonal antibodies against a retinal guidance molecule (RGM) protein

• US 9,175,075 B2
• Filed: 12/08/2010
• Issued: 11/03/2015
• Est. Priority Date: 12/08/2009
• Status: Active Grant

• Current Assignee: Abbvie Deutschland GmbH & Company KG (Abbvie Incorporated)
• Original Assignee: Abbvie Deutschland GmbH & Company KG (Abbvie Incorporated)
• Inventors: Mueller, Bernhard K.
• Primary Examiner(s): WANG, CHANG YU
• Application Number:
  US12/963,461
• Publication Number:
  US 20110135664A1
• Time in Patent Office: 1,791 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• 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 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• 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: 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 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

Abstract

The present application describes RGM A binding proteins, particularly monoclonal antibodies, and in particular CDR grafted, humanized versions thereof, which have the ability to bind to RGM A and prevent binding of RGM proteins to RGM A receptor and other RGM A binding proteins, and therefore neutralize the function of RGM A, for use in the treatment of retinal nerve fiber layer (RNFL) degeneration as well as methods of therapeutically or prophylactically treating a mammal against RNFL degeneration.

Claims

1. A method of treating retinal nerve fiber layer (RNFL) degeneration, comprising the step of administering to a mammal in need thereof an effective amount of a composition comprising an isolated antibody, wherein the isolated antibody comprises an antigen binding domain, said antibody capable of binding an epitope of a retinal guidance molecule (RGM), said antigen binding domain comprising a heavy chain variable domain having three complementary determining regions and a light chain variable domain having three complementary determining regions, wherein the three complementary determining regions of the heavy chain variable domain have the amino acid sequence of SEQ ID NO:

57, SEQ ID NO;

58 and SEQ ID NO;

59 and the three complementary determining regions of the light chain variable domain have the amino acid sequence of SEQ ID NO;

60, SEQ ID NO;

61 and SEQ ID NO;

62.

2. The method of claim 1, wherein said treatment is an therapeutic, neuroregenerative or neuroprotective, local or systemic treatment.

3. The method of claim 1, wherein the antibody is a monoclonal antibody, a chimeric antibody or a humanized antibody.

4. The method of claim 1, wherein said antibody further comprises a human acceptor framework, and wherein said human acceptor framework comprises at least one amino acid sequence selected from the group consisting of:

SEQ ID NO;

15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32 and 33.

5. The method of claim 4, wherein the antibody is a monoclonal antibody, a chimeric antibody or a humanized antibody.

6. A method of treating retinal nerve fiber layer (RNFL) degeneration, comprising the step of administering to a mammal in need thereof an effective amount of a composition comprising an isolated antibody,

wherein the isolated antibody comprises an antigen binding domain, said antibody capable of binding an epitope of a retinal guidance molecule (RGM), said antigen binding domain comprising a heavy chain variable domain and a light chain variable domain selected from the group consisting of:

(a) the heavy chain variable domain having the amino acid sequence of SEQ ID NO;

47 and the light chain variable domain having the amino acid sequence of SEQ ID NO;

44,

(b) heavy chain variable domain having the amino acid sequence of SEQ ID NO;

48 and the light chain variable domain having the amino acid sequence of SEQ ID NO;

44,

(c) the heavy chain variable domain having the amino acid sequence of SEQ ID NO;

49 and the light chain variable domain having the amino acid sequence of SEQ ID NO;

44,

(d) the heavy chain variable domain having the amino acid sequence of SEQ ID NO;

50 and the light chain variable domain having the amino acid sequence of SEQ ID NO;

44,

(e) the heavy chain variable domain having the amino acid sequence of SEQ ID NO;

47 and the light chain variable domain having the amino acid sequence of SEQ ID NO;

45,

(f) the heavy chain variable domain having the amino acid sequence of SEQ ID NO;

48 and the light chain variable domain having the amino acid sequence of SEQ ID NO;

45,

(g) the heavy chain variable domain having the amino acid sequence of SEQ ID NO;

49 and the light chain variable domain having the amino acid sequence of SEQ ID NO;

45,

(h) the heavy chain variable domain having the amino acid sequence of SEQ ID NO;

50 and the light chain variable domain having the amino acid sequence of SEQ ID NO;

45,

(i) the heavy chain variable domain having the amino acid sequence of SEQ ID NO;

47 and the light chain variable domain having the amino acid sequence of SEQ ID NO;

46,

(j) the heavy chain variable domain having the amino acid sequence of SEQ ID NO;

48 and the light chain variable domain having the amino acid sequence of SEQ ID NO;

46,

(k) the heavy chain variable domain having the amino acid sequence of SEQ ID NO;

49 and the light chain variable domain having the amino acid sequence of SEQ ID NO;

46,

(l) the heavy chain variable domain having the amino acid sequence of SEQ ID NO;

50 and the light chain variable domain having the amino acid sequence of SEQ ID NO;

46,

(m) the heavy chain variable domain having the amino acid sequence of SEQ ID NO;

48 and the light chain variable domain having the amino acid sequence of SEQ ID NO;

51,

(n) the heavy chain variable domain having the amino acid sequence of SEQ ID NO;

48 and the light chain variable domain having the amino acid sequence of SEQ ID NO;

52,

(o) the heavy chain variable domain having the amino acid sequence of SEQ ID NO;

48 and the light chain variable domain having the amino acid sequence of SEQ ID NO;

53,

(p) the heavy chain variable domain having the amino acid sequence of SEQ ID NO;

48 and the light chain variable domain having the amino acid sequence of SEQ ID NO;

54,

(q) the heavy chain variable domain having the amino acid sequence of SEQ ID NO;

50 and the light chain variable domain having the amino acid sequence of SEQ ID NO;

51,

(r) the heavy chain variable domain having the amino acid sequence of SEQ ID NO;

50 and the light chain variable domain having the amino acid sequence of SEQ ID NO;

52,

(s) the heavy chain variable domain having the amino acid sequence of SEQ ID NO;

50 and the light chain variable domain having the amino acid sequence of SEQ ID NO;

53, and

(t) the heavy chain variable domain having the amino acid sequence of SEQ ID NO;

50 and the light chain variable domain having the amino acid sequence of SEQ ID NO;

54.

7. The method of claim 6, wherein said treatment is an therapeutic, neuroregenerative or neuroprotective, local or systemic treatment.

8. The method of claim 6, wherein the antibody is a monoclonal antibody, a chimeric antibody or a humanized antibody.