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

• US 20130330347A1
• Filed: 01/25/2013
• Published: 12/12/2013
• Est. Priority Date: 01/27/2012
• Status: Abandoned Application

• Current Assignee: Abbvie Incorporated
• Original Assignee: Abbvie Deutschland GmbH & Company KG (Abbvie Incorporated), Abbvie Incorporated
• Inventors: Mueller, Bernhard, Kutskova, Yuliya, Memmott, John, Huang, Lili, Bardwell, Philip D.
• Application Number:
  US13/750,846
• Publication Number:
  US 20130330347A1
• Time in Patent Office: Days
• US Class Current: 424/139.1
• 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. An isolated antibody or antibody fragment thereof which binds to Repulsive Guidance Molecule a (“

RGMa”

), wherein the antibody comprises a domain or region selected from the group consisting of;

(a) a variable heavy domain region comprising the amino acid sequence of SEQ ID NO;

1, (b) a variable light domain region comprising the amino acid sequence of SEQ ID NO;

5, (c) a variable heavy domain region comprising the amino acid sequence of SEQ ID NO;

9, (d) a variable light domain region comprising the amino acid sequence of SEQ ID NO;

13, (e) a variable heavy domain region comprising the amino acid sequence of SEQ ID NO;

17, (f) a variable light domain region comprising the amino acid sequence of SEQ ID NO;

21, (g) a variable heavy domain region comprising the amino acid sequence of SEQ ID NO;

25, (h) a variable light domain region comprising the amino acid sequence of SEQ ID NO;

29, (i) a variable heavy domain region comprising the amino acid sequence of SEQ ID NO;

33, (j) a variable light domain region comprising the amino acid sequence of SEQ ID NO;

37;

(k) a variable heavy domain region comprising the amino acid sequence of SEQ ID NO;

41;

(l) a variable light domain region comprising the amino acid sequence of SEQ ID NO;

45;

(m) a variable heavy domain region comprising the amino acid sequence of SEQ ID NO;

49;

(n) a variable light domain region comprising the amino acid sequence of SEQ ID NO;

53, (o) a variable heavy domain region comprising the amino acid sequence of SEQ ID NO;

57, (p) a variable light domain region comprising the amino acid sequence of SEQ ID NO;

61, (q) a variable heavy domain region comprising the amino acid sequence of SEQ ID NO;

152, (r) a variable light domain region comprising the amino acid sequence of SEQ ID NO;

95, (s) a variable heavy domain region comprising the amino acid sequence of SEQ ID NO;

99, (t) a variable light domain region comprising the amino acid sequence of SEQ ID NO;

103, (u) a variable heavy domain region comprising the amino acid sequence of SEQ ID NO;

107, (v) a variable light domain region comprising the amino acid sequence of SEQ ID NO;

111, (w) a variable heavy domain region comprising the amino acid sequence of SEQ ID NO;

115, (x) a variable light domain region comprising the amino acid sequence of SEQ ID NO;

119, (y) a variable heavy domain region comprising the amino acid sequence of SEQ ID NO;

123, (z) a variable light domain region comprising the amino acid sequence of SEQ ID NO;

127, (aa) a variable heavy domain region comprising the amino acid sequence of SEQ ID NO;

131, (bb) a variable light domain region comprising the amino acid sequence of SEQ ID NO;

135, (cc) a variable light domain region comprising the amino acid sequence of SEQ ID NO;

67, (dd) a variable light domain region comprising the amino acid sequence of SEQ ID NO;

68, (ee) a variable light domain region comprising the amino acid sequence of SEQ ID NO;

69 (ff) a variable light domain region comprising the amino acid sequence of SEQ ID NO;

70, (gg) a variable light domain region comprising the amino acid sequence of SEQ ID NO;

71, (hh) a variable light domain region comprising the amino acid sequence of SEQ ID NO;

72, (ii) a variable light domain region comprising the amino acid sequence of SEQ ID NO;

73, (jj) a variable heavy domain comprising the amino acid sequence of SEQ ID NO;

1 and a variable light domain region comprising the amino acid sequence of SEQ ID NO;

5, (kk) a variable heavy domain comprising the amino acid sequence of SEQ ID NO;

9 and a variable light domain region comprising the amino acid sequence of SEQ ID NO;

13, (ll) a variable heavy domain comprising the amino acid sequence of SEQ ID NO;

17 and a variable light domain region comprising the amino acid sequence of SEQ ID NO;

21, (mm) a variable heavy domain comprising the amino acid sequence of SEQ ID NO;

25 and a variable light domain region comprising the amino acid sequence of SEQ ID NO;

29, (nn) a variable heavy domain comprising the amino acid sequence of SEQ ID NO;

33 and a variable light domain region comprising the amino acid sequence of SEQ ID NO;

37, (oo) a variably heavy domain comprising the amino acid sequence of SEQ ID NO;

41 and a variable light domain region comprising the amino acid sequence of SEQ ID NO;

45, (pp) a variable heavy domain comprising the amino acid sequence of SEQ ID NO;

49 and a variable light domain region comprising the amino acid sequence of SEQ ID NO;

53, (qq) a variable heavy domain comprising the amino acid sequence of SEQ ID NO;

57 and a variable light domain region comprising the amino acid sequence of SEQ ID NO;

61, (rr) a variable heavy domain region comprising the amino acid sequence of SEQ ID NO;

152 and a variable light domain region comprising the amino acid sequence of SEQ ID NO;

95, (ss) a variable heavy domain region comprising the amino acid sequence of SEQ ID NO;

99 and a variable light domain region comprising the amino acid sequence of SEQ ID NO;

103, (tt) a variable heavy domain region comprising the amino acid sequence of SEQ ID NO;

107 and a variable light domain region comprising the amino acid sequence of SEQ ID NO;

111, (uu) a variable heavy domain region comprising the amino acid sequence of SEQ ID NO;

115 and a variable light domain region comprising the amino acid sequence of SEQ ID NO;

119, (vv) a variable heavy domain region comprising the amino acid sequence of SEQ ID NO;

123 and a variable light domain region comprising the amino acid sequence of SEQ ID NO;

127, (ww) a variable heavy domain region comprising the amino acid sequence of SEQ ID NO;

131 and a variable light domain region comprising the amino acid sequence of SEQ ID NO;

135, (xx) a variable heavy chain 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, (yy) a variable light chain 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, (zz) a variable heavy chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO;

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

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

12, (aaa) a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO;

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

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

16, (bbb) a variable heavy chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO;

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

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

20, (ccc) a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO;

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

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

24, (ddd) a variable heavy chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO;

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

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

28, (eee) a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO;

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

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

32, (fff) a variable heavy chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO;

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

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

36, (ggg) a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO;

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

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

40, (hhh) a variable heavy chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO;

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

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

44;

(iii) a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO;

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

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

48;

(jjj) a variable heavy chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO;

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

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

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

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

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

56, (kkk) a variable heavy chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO;

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

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

60, (lll) a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO;

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

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

64, (mmm) a variable heavy chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO;

92 or 153, a CDR2 comprising the amino acid sequence of SEQ ID NO;

93 or 154, and a CDR3 comprising the amino acid sequence of SEQ ID NO;

94 or 155, (nnn) a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO;

96 or 156, a CDR2 comprising the amino acid sequence of SEQ ID NO;

97 or 157, and a CDR3 comprising the amino acid sequence of SEQ ID NO;

98 or 158, (ooo) a variable heavy chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO;

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

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

102, (ppp) a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO;

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

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

106, (qqq) a variable heavy chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO;

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

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

110, (rrr) a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO;

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

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

114, (sss) a variable heavy chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO;

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

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

118, (ttt) a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO;

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

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

122, (uuu) a variable heavy chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO;

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

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

126, (vvv) a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO;

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

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

130, (www) a variable heavy chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO;

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

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

134, (xxx) a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO;

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

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

138, (yyy) a variable light chain 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;

67, (zzz) a variable light chain 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;

68, (aaaa) a variable light chain 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;

69, (bbbb) a variable light chain 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;

70, (cccc) a variable light chain 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;

71, (dddd) a variable light chain 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;

72, (eeee) a variable light chain 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;

73, (ffff) a variable heavy chain comprising a CDR1 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 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, (gggg) a variable heavy chain comprising a CDR1 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 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;

67, (hhhh) a variable heavy chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO;

92 or 153, a CDR2 comprising the amino acid sequence of SEQ ID NO;

93 or 154, and a CDR3 comprising the amino acid sequence of SEQ ID NO;

94 or 155 and a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO;

96 or 156, a CDR2 comprising the amino acid sequence of SEQ ID NO;

97 or 157, and a CDR3 comprising the amino acid sequence of SEQ ID NO;

98 or 158, (iiii) a variable heavy chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO;

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

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

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

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

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

106, (jjjj) a variable heavy chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO;

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

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

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

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

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

114, (kkkk) a variable heavy chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO;

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

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

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

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

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

122, (llll) a variable heavy chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO;

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

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

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

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

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

130, (mmmm) a variable heavy chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO;

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

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

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

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

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

138, (nnnn) a variable heavy chain comprising a CDR1 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 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;

68, (oooo) a variable heavy chain comprising a 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 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;

69, (pppp) a variable heavy chain comprising a 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 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;

70, (qqqq) a variable heavy chain comprising a 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 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;

71, (rrrr) a variable heavy chain comprising a 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 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;

72, (ssss) a variable heavy chain comprising a 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 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;

73, (tttt) a variable heavy chain comprising a CDR 1 comprising the amino acid sequence of SEQ ID NO;

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

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

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

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

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

16, (uuuu) a variable heavy chain comprising a CDR 1 comprising the amino acid sequence of SEQ ID NO;

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

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

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

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

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

24, (vvvv) a variable heavy chain comprising a CDR 1 comprising the amino acid sequence of SEQ ID NO;

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

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

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

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

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

32, (wwww) a variable heavy chain comprising a CDR 1 comprising the amino acid sequence of SEQ ID NO;

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

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

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

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

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

40, (xxxx) a variable heavy domain chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO;

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

43, and a CDR comprising the amino acid sequence of SEQ ID NO;

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

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

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

48;

(yyyy) a variable heavy chain comprising a CDR 1 comprising the amino acid sequence of SEQ ID NO;

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

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

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

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

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

56, (zzzz) a variable heavy chain comprising a CDR 1 comprising the amino acid sequence of SEQ ID NO;

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

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

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

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

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

64.

2. The isolated antibody or antibody fragment of claim 1, 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, 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.

4. The isolated antibody or antibody fragment of claim 1, wherein the monoclonal antibody or antibody fragment comprises a heavy chain immunoglobulin constant domain selected from the group consisting of a human IgM constant domain, a human IgG4 constant domain, a human IgG1 constant domain, a human IgE constant domain, a human IgG2 constant domain, a human IgG3 constant domain, and a human IgA constant domain.

5. The isolated antibody or antibody fragment of claim 4, wherein the human IgG1 constant domain comprises SEQ ID NO:

140.

7. The isolated antibody or antibody fragment of claim 1, wherein the antibody or antibody fragment comprises:

(1) a variable heavy region comprising a sequence selected from the group consisting of SEQ ID NO;

1, SEQ ID NO;

9, SEQ ID NO;

17, SEQ ID NO;

25, SEQ ID NO;

33, SEQ ID NO;

41, SEQ ID NO;

49, SEQ ID NO;

57, SEQ ID NO;

91, SEQ ID NO;

99, SEQ ID NO;

107, SEQ ID NO;

115, SEQ ID NO;

123, and SEQ ID NO;

131;

or (2) a variable light region comprising a sequence selected from the group consisting of SEQ ID NO;

5, SEQ ID NO;

13, SEQ ID NO;

21, SEQ ID NO;

29, SEQ ID NO;

37, SEQ ID NO;

45, SEQ ID NO;

53, SEQ ID NO;

61, SEQ ID NO;

95, SEQ ID NO;

103, SEQ ID NO;

111, SEQ ID NO;

119, SEQ ID NO;

127, and SEQ ID NO;

135.

9. The isolated antibody or antibody fragment of claim 1, wherein the antibody or antibody fragment comprises:

(1) a variable light domain that comprises complementarity-determining region (CDR) residues SEQ ID NO;

6, SEQ ID NO;

7, and SEQ ID NO;

8, or SEQ ID NO;

6, SEQ ID NO;

7, and SEQ ID NO;

67, SEQ ID NO;

6, SEQ ID NO;

7, and SEQ ID NO;

68, or SEQ ID NO;

6, SEQ ID NO;

7, and SEQ ID NO;

69, or SEQ ID NO;

6, SEQ ID NO;

7, and SEQ ID NO;

70, or SEQ ID NO;

6, SEQ ID NO;

7, and SEQ ID NO;

71, or SEQ ID NO;

6, SEQ ID NO;

7, and SEQ ID NO;

72 or SEQ ID NO;

6, SEQ ID NO;

7, and SEQ ID NO;

73, or SEQ ID NO;

14, SEQ ID NO;

15, and SEQ ID NO;

16, or SEQ ID NO;

22, SEQ ID NO;

23, and SEQ ID NO;

24, or SEQ ID NO;

30, SEQ ID NO;

31, and SEQ ID NO;

32, or SEQ ID NO;

38, SEQ ID NO;

39, and SEQ ID NO;

40, or SEQ ID NO;

54, SEQ ID NO;

55, and SEQ ID NO;

56, or SEQ ID NO;

62, SEQ ID NO;

63, and SEQ ID NO;

64, or SEQ ID NO;

46, SEQ ID NO;

47, and SEQ ID NO;

48, SEQ ID NO;

96, SEQ ID NO;

97, and SEQ ID NO;

98, SEQ ID NO;

104, SEQ ID NO;

105, and SEQ ID NO;

106, SEQ ID NO;

112, SEQ ID NO;

113, and SEQ ID NO;

114, SEQ ID NO;

120, SEQ ID NO;

121, and SEQ ID NO;

122, SEQ ID NO;

128, SEQ ID NO;

129, and SEQ ID NO;

130, SEQ ID NO;

136, SEQ ID NO;

137, and SEQ ID NO;

138, and SEQ ID NO;

156, and SEQ ID NO;

157, and SEQ ID NO;

158;

or (2) a variable heavy domain that comprises complementarity-determining region (CDR) residues SEQ ID NO;

2, SEQ ID NO;

3, and SEQ ID NO;

4, or SEQ ID NO;

10, SEQ ID NO;

11, and SEQ ID NO;

12, or SEQ ID NO;

18, SEQ ID NO;

19, and SEQ ID NO;

20, or SEQ ID NO;

26, SEQ ID NO;

27, and SEQ ID NO;

28, or SEQ ID NO;

34, SEQ ID NO;

35, and SEQ ID NO;

36, or SEQ ID NO;

50, SEQ ID NO;

51, and SEQ ID NO;

52, or SEQ ID NO;

58, SEQ ID NO;

59, and SEQ ID NO;

60, SEQ ID NO;

42, SEQ ID NO;

43, and SEQ ID NO;

44, SEQ ID NO;

92, SEQ ID NO;

93, and SEQ ID NO;

94, SEQ ID NO;

100, SEQ ID NO;

101, and SEQ ID NO;

102, SEQ ID NO;

108, SEQ ID NO;

109, and SEQ ID NO;

110, SEQ ID NO;

116, SEQ ID NO;

117, and SEQ ID NO;

118, SEQ ID NO;

124, SEQ ID NO;

125, and SEQ ID NO;

126, SEQ ID NO;

132, SEQ ID NO;

133, and SEQ ID NO;

134, and SEQ ID NO;

153, and SEQ ID NO;

154, and SEQ ID NO;

155.

11. The isolated antibody or antibody fragment of claim 1, wherein the antibody or antibody fragment comprises:

(1) a variable heavy domain that comprises complementarity-determining region (CDR) residues SEQ ID NO;

2, SEQ ID NO;

3, and SEQ ID NO;

4, and a variable light domain that comprises complementarity-determining region (CDR) residues SEQ ID NO;

6, SEQ ID NO;

7, and SEQ ID NO;

8;

(2) a variable heavy domain that comprises complementarity-determining region (CDR) residues SEQ ID NO;

10, SEQ ID NO;

11, and SEQ ID NO;

12, and a variable light domain that comprises complementarity-determining region (CDR) residues SEQ ID NO;

14, SEQ ID NO;

15, and SEQ ID NO;

16, (3) a variable heavy domain that comprises complementarity-determining region (CDR) residues SEQ ID NO;

18, SEQ ID NO;

19, and SEQ ID NO;

20, and a variable light domain that comprises complementarity-determining region (CDR) residues SEQ ID NO;

22, SEQ ID NO;

23, and SEQ ID NO;

24, (4) a variable heavy domain that comprises complementarity-determining region (CDR) residues SEQ ID NO;

26, SEQ ID NO;

27, and SEQ ID NO;

28, and a variable light domain that comprises complementarity-determining region (CDR) residues SEQ ID NO;

30, SEQ ID NO;

31, and SEQ ID NO;

32, (5) a variable heavy domain that comprises complementarity-determining region (CDR) residues SEQ ID NO;

34, SEQ ID NO;

35, and SEQ ID NO;

36, and a variable light domain that comprises complementarity-determining region (CDR) residues SEQ ID NO;

38, SEQ ID NO;

39, and SEQ ID NO;

40;

(6) a variable heavy domain that comprises complementarity-determining region (CDR) residues SEQ ID NO;

50, SEQ ID NO;

51, and SEQ ID NO;

52, and a variable light domain that comprises complementarity-determining region (CDR) residues SEQ ID NO;

54, SEQ ID NO;

55, and SEQ ID NO;

56, (7) a variable heavy domain that comprises complementarity-determining region (CDR) residues SEQ ID NO;

58, SEQ ID NO;

59, and SEQ ID NO;

60, and a variable light domain that comprises complementarity-determining region (CDR) residues SEQ ID NO;

62, SEQ ID NO;

63, and SEQ ID NO;

64;

(8) a variable heavy domain that comprises complementarity-determining region (CDR) residues SEQ ID NO;

42, SEQ ID NO;

43, and SEQ ID NO;

44, and a variable light domain that comprises complementarity-determining region (CDR) residues SEQ ID NO;

46, SEQ ID NO;

47, and SEQ ID NO;

48 (9) a variable heavy domain that comprises complementarity-determining region (CDR) residues SEQ ID NO;

92 or 153, SEQ ID NO;

93 or 154, and SEQ ID NO;

94 or 155, and a variable light domain that comprises complementarity-determining region (CDR) residues SEQ ID NO;

96 or 156, SEQ ID NO;

97 or 157, and SEQ ID NO;

98 or 158, (10) a variable heavy domain that comprises complementarity-determining region (CDR) residues SEQ ID NO;

100, SEQ ID NO;

101, and SEQ ID NO;

102, and a variable light domain that comprises complementarity-determining region (CDR) residues SEQ ID NO;

104, SEQ ID NO;

105, and SEQ ID NO;

106, (11) a variable heavy domain that comprises complementarity-determining region (CDR) residues SEQ ID NO;

108, SEQ ID NO;

109, and SEQ ID NO;

110, and a variable light domain that comprises complementarity-determining region (CDR) residues SEQ ID NO;

112, SEQ ID NO;

113, and SEQ ID NO;

114, (12) a variable heavy domain that comprises complementarity-determining region (CDR) residues SEQ ID NO;

116, SEQ ID NO;

117, and SEQ ID NO;

118, and a variable light domain that comprises complementarity-determining region (CDR) residues SEQ ID NO;

120, SEQ ID NO;

121, and SEQ ID NO;

122, (13) a variable heavy domain that comprises complementarity-determining region (CDR) residues SEQ ID NO;

124, SEQ ID NO;

125, and SEQ ID NO;

126, and a variable light domain that comprises complementarity-determining region (CDR) residues SEQ ID NO;

128, SEQ ID NO;

129, and SEQ ID NO;

130, or (14) a variable heavy domain that comprises complementarity-determining region (CDR) residues SEQ ID NO;

132, SEQ ID NO;

133, and SEQ ID NO;

134, and a variable light domain that comprises complementarity-determining region (CDR) residues SEQ ID NO;

136, SEQ ID NO;

137, and SEQ ID NO;

138.

25. The antibody or antibody fragment of claim 1, wherein the antibody or antibody fragment further comprises an agent selected from the group consisting of:

an immunoadhesion molecule, an imaging agent, and a therapeutic agent.

26. The antibody or antibody fragment of claim 25, 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.

28. A pharmaceutical composition comprising the antibody, antibody fragment, mixture or derivative thereof of claim 1.

29. A method of treating, preventing, modulating, or attenuating a disease or disorder associated with neurite degeneration, comprising administering to a subject in need thereof a therapeutically effective amount of the antibody of claim 1.

30. The method of claim 29, wherein the neurite degenerative disorder is selected from the group consisting of multiple sclerosis, Parkinson'"'"'s disease, Alzheimer'"'"'s disease, Tay-Sachs disease, Niemann-Pick disease, Gaucher'"'"'s disease, Hurler'"'"'s syndrome, Huntington'"'"'s disease, amyotrophic lateral sclerosis, idiopathic inflammatory demyelinating diseases, vitamin B12 deficiency, central pontine myelinolysis, tabes dorsalis, transverse myelitis, Devic'"'"'s disease, progressive multifocal leukoencephalopathy, optic neuritis, traumatic injury to the CNS, an ischemic cerebral stroke, glaucoma, diabetic retinopathy, age-dependent macular degeneration, and a leukodystrophy.

37. The isolated antibody or antibody fragment of claim 1, wherein the antibody or antibody fragment comprises SEQ ID NOs:

1-7 and 67, 68, 69, 70, 71, 72 or 73.

44. The isolated antibody of any one of claim 37, wherein the isolated antibody binds to the RGMa epitope PCKILKCNSEFWSATSGSHAPAS (hRGMa 47-69) (SEQ ID NO:

79).

3. (canceled)

6. (canceled)

8. (canceled)

10. (canceled)

12. (canceled)

13. (canceled)

14. (canceled)

15. (canceled)

16. (canceled)

17. (canceled)

18. (canceled)

19. (canceled)

20. (canceled)

21. (canceled)

22. (canceled)

23. (canceled)

24. (canceled)

27. (canceled)

31. A method for determining whether a subject has a neurite degenerative disorder, comprising

(a) measuring the level of RGMa in a sample from the subject;

and

(b) comparing the level of RGMa in the sample with a normal control, wherein an altered level of RGMa indicates that the subject has a neurite degenerative disorder.

32. The method of claim 31, wherein an increased level of RGMa as compared to the normal control, indicates that the subject has neurite degenerative disorder.

33. The method of claim 31, wherein the sample is selected from the group consisting of a blood sample, a cerebrospinal fluid sample, and a serum sample.

34. The method of claim 31, wherein step (a) is an immunoassay.

35. The method of claim 35, wherein the immunoassay is an enzyme-linked immunosorbent assay (ELISA).

36. The method of claim 35, wherein the ELISA is a sandwich ELISA.

38. (canceled)

39. (canceled)

40. (canceled)

41. (canceled)

42. (canceled)

43. (canceled)

45. An isolated antibody or antibody fragment thereof which binds to Repulsive Guidance Molecule a (“

RGMa”

), wherein the antibody or antibody fragment comprises a variable heavy domain that comprises three complementarity-determining regions (CDR) corresponding to the following formulas, respectively;

Xaa1-Xaa2-Xaa3-Xaa4-Xaa5 (Formula 1-CDR-H1), wherein Xaa1 is an amino acid selected from the group consisting of S, D, E, N, G, and T;

Xaa2 is an amino acid selected from the group consisting of H, Y, L, S, and Q;

Xaa3 is an amino acid selected from the group consisting of G, D, A, T, and Y;

Xaa4 is an amino acid selected from the group consisting of I, M, and W; and

Xaa5 is an amino acid sequence from the group consisting of S, N, H, A, T, and Q;

Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7-Xaa8-Xaa9-Xaa10-Xaa11-Xaa12-Xaa13-Xaa14-Xaa15-Xaa16-(Xaa)_n (Formula 2-CDR-H2), wherein n is 0 or 1, and

wherein Xaa1 is an amino acid selected from the group consisting of Y, V, A, G, L, G, S, and N;

Xaa2 is an amino acid selected from the group consisting of I, M, and F;

Xaa3 is an amino acid selected from the group consisting of S, N, D, F, and Y;

Xaa4 is an amino acid selected from the group consisting of P, Y, G, W, H, A, and S;

Xaa5 is an amino acid selected from the group consisting of Y, N, D, E, S, K, G, and T;

Xaa6 is an amino acid selected from the group consisting of S, G, D, T, and N;

Xaa7 is an amino acid selected from the group consisting of G, S, I, E, N, and R;

Xaa8 is an amino acid selected from the group consisting of N, L, R, S, T, and Y;

Xaa9 is an amino acid selected from the group consisting of T, K, G, N, I, and Y;

Xaa10 is an amino acid selected from the group consisting of N, G, Y, T, and K;

Xaa11 is an amino acid selected from the group consisting of Y, F, N, and H;

Xaa12 is an amino acid selected from the group consisting of A, T, V, P, L, and S;

Xaa13 is an amino acid selected from the group consisting of Q, D, P, and S;

Xaa14 is an amino acid selected from the group consisting of K, S, N, and L;

Xaa15 is an amino acid selected from the group consisting of L, F, V, K, and R;

Xaa16 is an amino acid selected from the group consisting of Q, K, R, and S; and

Xaa17 is a glycine; and

Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-(Xaa)_n (Formula 3-CDR-H3), wherein n is 0-11, and

wherein Xaa1 is an amino acid selected from the group consisting of V, S, E, N, L, D, Q, and A;

Xaa2 is an amino acid selected from the group consisting of G, T, R, Y, L, I, D, and S;

Xaa3 is an amino acid selected from the group consisting of S, V, D, G, F, Y, P, M, C, L, and A;

Xaa4 is an amino acid selected from the group consisting of G, L, Y, N, E, K, A, and F;

Xaa5 is an amino acid selected from the group consisting of P, S, Y, A, V, G, T, E, and W;

Xaa6 is an amino acid selected from the group consisting of Y, V, S, L, D, G, H, and P;

Xaa7 is an amino acid selected from the group consisting of Tyr, Asp, Gly, Ser, Phe, Leu, and Cys;

Xaa8 is an amino acid selected from the group consisting of Tyr, Lys, Asp, Ala, and Gln;

Xaa9 is an amino acid selected from the group consisting of Met, Glu, Phe, Leu, Ser, Thr, Pro, and Tyr;

Xaa10 is an amino acid selected from the group consisting of Asp, Gly, Tyr, Ser, Leu, His, and Phe;

Xaa11 is an amino acid selected from the group consisting of Val, Tyr, Leu, His, Gly, Trp, and Asp;

Xaa12 is an amino acid selected from the group consisting of Tyr and Phe;

Xaa13 is an amino acid selected from the group consisting of Tyr, Gly, and Asp;

Xaa14 is an amino acid selected from the group consisting of Ala, Leu, Pro, and Tyr;

Xaa15 is an amino acid selected from the group consisting of Met, Leu, and Phe;

Xaa16 is an amino acid selected from the group consisting of Asp and Gly; and

Xaa17 is an amino acid selected from the group consisting of an Val, Asp, and Tyr.

46. An isolated antibody or antibody fragment thereof which binds to Repulsive Guidance Molecule a (“

RGMa”

), wherein the antibody or antibody fragment comprises a variable light domain that comprises three complementarity-determining regions (CDR) corresponding to the following formulas, respectively;

Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7-Xaa8-Xaa9-Xaa10-Xaa11-(Xaa)_n (Formula 1-CDR-L1), wherein n is 0-3, and

wherein Xaa1 is an amino acid selected from the group consisting of T, S, R, G, and Q;

Xaa2 is an amino acid selected from the group consisting of G, L, and A;

Xaa3 is an amino acid selected from the group consisting of T, D, S, N and A;

Xaa4 is an amino acid selected from the group consisting of S, K, G, Q, N, and E;

Xaa5 is an amino acid sequence from the group consisting of S, L, G, I, D, and P;

Xaa6 is an amino acid selected from the group consisting of S, G, N, H, and I;

Xaa7 is an amino acid selected from the group consisting of V, D, I, S, G and H;

Xaa8 is an amino acid selected from the group consisting of G, K, A, S, I, N, T, and D;

Xaa9 is an amino acid selected from the group consisting of D, Y, A, C, S, and F;

Xaa10 is an amino acid selected from the group consisting of S, A, G, L, V, and N;

Xaa11 is an amino acid selected from the group consisting of I, C, Y, H, R, N, and S;

Xaa12 is an amino acid selected from the group consisting of Tyr, Gly, Ala, and Val;

Xaa13 is an amino acid selected from the group consisting of Val, and Asn; and

Xaa14 is an amino acid selected from the group consisting of Ser and His;

Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7-(Xaa)_n (Formula 2-CDR-L2), wherein n is 0-4, and wherein Xaa1 is an amino acid selected from the group consisting of D, Q, G, V, Y, S and E;

Xaa2 is an amino acid selected from the group consisting of V, D, N, and A;

Xaa3 is an amino acid selected from the group consisting of T, S, Y, N, and K;

Xaa4 is an amino acid selected from the group consisting of K, N, D, Q and T;

Xaa5 is an amino acid selected from the group consisting of R, G, S, and L;

Xaa6 is an amino acid selected from the group consisting of P, S, I, and E;

Xaa7 is an amino acid selected from the group consisting of S, H, I, and T;

Xaa8 is Asn;

Xaa9 is Lys; and

Xaa10 is Gly;

Xaa11 is Asp; and

Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7-Xaa8-Xaa9-(Xaa)_n (Formula 3-CDR-L3), wherein n is 0-2, and

wherein Xaa1 is an amino acid selected from the group consisting of C, Q, H, F, H, L, V, I, K, Y, and A;

Xaa2 is an amino acid selected from the group consisting of S, A, T, Q, and V;

Xaa3 is an amino acid selected from the group consisting of Y, W, and S;

Xaa4 is an amino acid selected from the group consisting of A, D, G, S, H and Y;

Xaa5 is an amino acid selected from the group consisting of G, S, N, P, D, V, and T;

Xaa6 is an amino acid selected from the group consisting of I, T, S, G, L, F and Y;

Xaa7 is an amino acid selected from the group consisting of D, T, L, I, P, and S;

Xaa8 is an amino acid selected from the group consisting of T, G, R, Y, D, N, W, L, F and P;

Xaa9 is an amino acid selected from the group consisting of L, V, G, T, and H;

Xaa10 is an amino acid selected from the group consisting of Val, Tyr, and His;

Xaa11 is Leu or Val.

47. An isolated antibody or antibody fragment thereof which binds to Repulsive Guidance Molecule a (“

RGMa”

), wherein the antibody or antibody fragment comprises a variable heavy domain that comprises three complementarity-determining regions (CDR-H1, H2, and H3) corresponding to the following formulas, respectively;

Xaa1-Xaa2-Xaa3-Xaa4-Xaa5 (Formula 1-CDR-H1), wherein Xaa1 is an amino acid selected from the group consisting of S, D, E, N, G, and T;

Xaa2 is an amino acid selected from the group consisting of H, Y, L, S, and Q;

Xaa3 is an amino acid selected from the group consisting of G, D, A, T, and Y;

Xaa4 is an amino acid selected from the group consisting of I, M, and W; and

Xaa5 is an amino acid sequence from the group consisting of S, N, H, A, T, and Q;

Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7-Xaa8-Xaa9-Xaa10-Xaa11-Xaa 12-Xaa13-Xaa14-Xaa15-Xaa16-(Xaa)_n (Formula 2-CDR-H2), wherein n is 0 or 1, and

wherein Xaa1 is an amino acid selected from the group consisting of Y, V, A, G, L, G, S, and N;

Xaa2 is an amino acid selected from the group consisting of I, M, and F;

Xaa3 is an amino acid selected from the group consisting of S, N, D, F, and Y;

Xaa4 is an amino acid selected from the group consisting of P, Y, G, W, H, A, and S;

Xaa5 is an amino acid selected from the group consisting of Y, N, D, E, S, K, G, and T;

Xaa6 is an amino acid selected from the group consisting of S, G, D, T, and N;

Xaa7 is an amino acid selected from the group consisting of G, S, I, E, N, and R;

Xaa8 is an amino acid selected from the group consisting of N, L, R, S, T, and Y;

Xaa9 is an amino acid selected from the group consisting of T, K, G, N, I, and Y;

Xaa10 is an amino acid selected from the group consisting of N, G, Y, T, and K;

Xaa11 is an amino acid selected from the group consisting of Y, F, N, and H;

Xaa12 is an amino acid selected from the group consisting of A, T, V, P, L, and S;

Xaa13 is an amino acid selected from the group consisting of Q, D, P, and S;

Xaa14 is an amino acid selected from the group consisting of K, S, N, and L;

Xaa15 is an amino acid selected from the group consisting of L, F, V, K, and R;

Xaa16 is an amino acid selected from the group consisting of Q, K, R, and S; and

Xaa17 is a glycine; and

Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-(Xaa)_n (Formula 3-CDR-H3), wherein n is 0-11, and

wherein Xaa1 is an amino acid selected from the group consisting of V, S, E, N, L, D, Q, and A;

Xaa2 is an amino acid selected from the group consisting of G, T, R, Y, L, I, D, and S;

Xaa3 is an amino acid selected from the group consisting of S, V, D, G, F, Y, P, M, C, L, and A;

Xaa4 is an amino acid selected from the group consisting of G, L, Y, N, E, K, A, and F;

Xaa5 is an amino acid selected from the group consisting of P, S, Y, A, V, G, T, E, and W;

Xaa6 is an amino acid selected from the group consisting of Y, V, S, L, D, G, H, and P;

Xaa7 is an amino acid selected from the group consisting of Tyr, Asp, Gly, Ser, Phe, Leu, and Cys;

Xaa8 is an amino acid selected from the group consisting of Tyr, Lys, Asp, Ala, and Gln;

Xaa9 is an amino acid selected from the group consisting of Met, Glu, Phe, Leu, Ser, Thr, Pro, and Tyr;

Xaa10 is an amino acid selected from the group consisting of Asp, Gly, Tyr, Ser, Leu, His, and Phe;

Xaa11 is an amino acid selected from the group consisting of Val, Tyr, Leu, His, Gly, Trp, and Asp;

Xaa12 is an amino acid selected from the group consisting of Tyr and Phe;

Xaa13 is an amino acid selected from the group consisting of Tyr, Gly, and Asp;

Xaa14 is an amino acid selected from the group consisting of Ala, Leu, Pro, and Tyr;

Xaa15 is an amino acid selected from the group consisting of Met, Leu, and Phe;

Xaa16 is an amino acid selected from the group consisting of Asp and Gly; and

Xaa17 is an amino acid selected from the group consisting of an Val, Asp, and Tyr; and

wherein the antibody or antibody fragment also comprises a variable light domain that comprises three complementarity-determining regions (CDR-L1, L2, and L3) corresponding to the following formulas, respectively;

Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7-Xaa8-Xaa9-Xaa10-Xaa11-(Xaa)_n (Formula 1-CDR-L1), wherein n is 0-3, and

wherein Xaa1 is an amino acid selected from the group consisting of T, S, R, G, and Q;

Xaa2 is an amino acid selected from the group consisting of G, L, and A;

Xaa3 is an amino acid selected from the group consisting of T, D, S, N and A;

Xaa4 is an amino acid selected from the group consisting of S, K, G, Q, N, and E;

Xaa5 is an amino acid sequence from the group consisting of S, L, G, I, D, and P;

Xaa6 is an amino acid selected from the group consisting of S, G, N, H, and I;

Xaa7 is an amino acid selected from the group consisting of V, D, I, S, G and H;

Xaa8 is an amino acid selected from the group consisting of G, K, A, S, I, N, T, and D;

Xaa9 is an amino acid selected from the group consisting of D, Y, A, C, S, and F;

Xaa10 is an amino acid selected from the group consisting of S, A, G, L, V, and N;

Xaa11 is an amino acid selected from the group consisting of I, C, Y, H, R, N, and S;

Xaa12 is an amino acid selected from the group consisting of Tyr, Gly, Ala, and Val;

Xaa13 is an amino acid selected from the group consisting of Val, and Asn; and

Xaa14 is an amino acid selected from the group consisting of Ser and His;

Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7-(Xaa)_n (Formula 2-CDR-L2), wherein n is 0-4, and wherein Xaa1 is an amino acid selected from the group consisting of D, Q, G, V, Y, S and E;

Xaa2 is an amino acid selected from the group consisting of V, D, N, and A;

Xaa3 is an amino acid selected from the group consisting of T, S, Y, N, and K;

Xaa4 is an amino acid selected from the group consisting of K, N, D, Q and T;

Xaa5 is an amino acid selected from the group consisting of R, G, S, and L;

Xaa6 is an amino acid selected from the group consisting of P, S, I, and E;

Xaa7 is an amino acid selected from the group consisting of S, H, I, and T;

Xaa8 is Asn;

Xaa9 is Lys; and

Xaa10 is Gly;

Xaa11 is Asp; and

Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7-Xaa8-Xaa9-(Xaa)_n (Formula 3-CDR-L3), wherein n is 0-2, and

wherein Xaa1 is an amino acid selected from the group consisting of C, Q, H, F, H, L, V, I, K, Y, and A;

Xaa2 is an amino acid selected from the group consisting of S, A, T, Q, and V;

Xaa3 is an amino acid selected from the group consisting of Y, W, and S;

Xaa4 is an amino acid selected from the group consisting of A, D, G, S, H and Y;

Xaa5 is an amino acid selected from the group consisting of G, S, N, P, D, V, and T;

Xaa6 is an amino acid selected from the group consisting of I, T, S, G, L, F and Y;

Xaa7 is an amino acid selected from the group consisting of D, T, L, I, P, and S;

Xaa8 is an amino acid selected from the group consisting of T, G, R, Y, D, N, W, L, F and P;

Xaa9 is an amino acid selected from the group consisting of L, V, G, T, and H;

Xaa10 is an amino acid selected from the group consisting of Val, Tyr, and His;

Xaa11 is Leu or Val.