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US 2017/0247448 A1Published application
Humanized anti-hepcidin antibodies and uses thereof
AssigneeIntrinsic Lifesciences LLC
InventorMark WESTERMAN
Life of this patent
Estimating the term…
Abstract
The present application relates to humanized antibodies that specifically bind to hepcidin and methods of using the humanized antibodies. Another aspect relates to humanized antibodies which bind hepcidin and regulate iron homeostasis. Another aspect relates to the use of humanized antibodies which bind hepcidin for the treatment of a disease or condition associated with hepcidin.
Claims46
A humanized antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region having an amino acid sequence set forth as SEQ ID NO:
- 42 and a light chain variable region having an amino acid sequence set forth as SEQ ID NO:
- 49, wherein:
- said heavy chain variable region comprises:
- (i) a CDR1 having an amino acid sequence of SEQ ID NO:
- 57, a CDR2 having an amino acid sequence of SEQ ID NO:
- 59, and a CDR3 having an amino acid sequence of SEQ ID NO:
- 61;
- (ii) a heavy chain FR1 having the amino acid sequence of SEQ ID NO:
- 56 or the amino acid sequence of SEQ ID NO:
- 56 except for one or more substitutions selected from the group consisting of:
- (a) a substitution of glutamine (Q) by glutamic acid (E) at position 1 utilizing the Kabat numbering system;
- (b) a substitution of isoleucine (I) by valine (V) at position 2 utilizing the Kabat numbering system;
- (c) a substitution of Proline (P) by alanine (A) at position 9 utilizing the Kabat numbering system;
- (d) a substitution of leucine (L) by valine (V) at position 11 utilizing the Kabat numbering system;
- (e) a substitution of glutamic acid (E) by alanine (A) at position 16 utilizing the Kabat numbering system;
- (f) a substitution of threonine (T) by serine (S) at position 17 utilizing the Kabat numbering system;
- (g) a substitution of valine (V) by leucine (L) at position 18 utilizing the Kabat numbering system;
- (h) a substitution of lysine (K) by arginine (R) at position 19 utilizing the Kabat numbering system;
- (i) a substitution of isoleucine (I) by valine (V) at position 20 utilizing the Kabat numbering system;
- and
- (j) a substitution of alanine (A) by glycine (G) at position 24 utilizing the Kabat numbering system;
- (iii) a heavy chain FR2 having the amino acid sequence of SEQ ID NO:
- 58 or the amino acid sequence of SEQ ID NO:
- 58 except for one or more substitutions selected from the group consisting of:
- (a) a substitution of valine (V) by isoleucine (I) at position 37 utilizing the Kabat numbering system;
- (b) a substitution of lysine (K) by arginine (R) at position 38 utilizing the Kabat numbering system;
- (c) a substitution of alanine (A) by proline (P) at position 40 utilizing the Kabat numbering system;
- (d) a substitution of proline (P) by arginine (R) or threonine (T) at position 41 utilizing the Kabat numbering system;
- (e) a substitution of lysine (K) by glutamine (Q) at position 43 utilizing the Kabat numbering system;
- (f) a substitution of glycine (G) by arginine (R) at position 44 utilizing the Kabat numbering system;
- (g) a substitution of lysine (K) by glutamic acid (E) at position 46 utilizing the Kabat numbering system;
- and
- (h) a substitution of methionine (M) by isoleucine (I) at position 48 utilizing the Kabat numbering system;
- (iv) a heavy chain FR3 having the amino acid sequence of SEQ ID NO:
- 60 or the amino acid sequence of SEQ ID NO:
- 60 except for one or more substitutions selected from the group consisting of:
- (a) a substitution of phenylalanine (F) for leucine (L) or valine (V) at position 68 utilizing the Kabat numbering system;
- (b) a substitution of alanine (A) for threonine (T) or valine (V) at position 69 utilizing the Kabat numbering system;
- (c) a substitution of phenylalanine (F) for isoleucine (I) at position 70 utilizing the Kabat numbering system;
- (d) a substitution of leucine (L) for lysine (K) or alanine (A) at position 72 utilizing the Kabat numbering system;
- (e) a substitution of glutamic acid (E) for aspartic acid (D) at position 73 utilizing the Kabat numbering system;
- (f) a substitution of threonine (T) for lysine (K) at position 74 utilizing the Kabat numbering system;
- (g) a substitution of alanine (A) for lysine (K), isoleucine (I) or valine (V) at position 76 utilizing the Kabat numbering system;
- (h) a substitution of serine (S) for asparagine (N) at position 77 utilizing the Kabat numbering system;
- (i) a substitution of threonine (T) for glutamine (Q) at position 78 utilizing the Kabat numbering system;
- (j) a substitution of alanine (A) for valine (V) at position 79 utilizing the Kabat numbering system;
- (k) a substitution of tyrosine (Y) for valine (V) at position 80 utilizing the Kabat numbering system;
- (l) a substitution of glutamine (Q) for threonine (T) at position 82 utilizing the Kabat numbering system;
- (m) a substitution of isoleucine (I) for methionine (M) or tryptophan (W) at position 83 utilizing the Kabat numbering system;
- (n) a substitution of asparagine (N) for threonine (T), serine (S) or cysteine (C) at position 84 utilizing the Kabat numbering system;
- (o) a substitution of asparagine (N) for serine (S) at position 85 utilizing the Kabat numbering system;
- (p) a substitution of leucine (L) for methionine (M) at position 86 utilizing the Kabat numbering system;
- (q) a substitution of lysine (K) for aspartic acid (D) at position 87 utilizing the Kabat numbering system;
- (r) a substitution of asparagine (N) for proline (P) or alanine (A) at position 88 utilizing the Kabat numbering system;
- (s) a substitution of glutamic acid (E) for valine (V) or serine (S) at position 89 utilizing the Kabat numbering system;
- (t) a substitution of threonine (T) for methionine (M) or valine (V) at position 93 utilizing the Kabat numbering system;
- and
- (u) a substitution of phenylalanine (F) for tyrosine (Y) at position 95 utilizing the Kabat numbering system;
- and
- (v) a heavy chain FR4 having the amino acid sequence of SEQ ID NO:
- 62 or the amino acid sequence of SEQ ID NO:
- 62 except for one or more conservative substitutions;
- and said light chain variable region comprises:
- (i) a CDR1 having an amino acid sequence of SEQ ID NO:
- 64, a CDR2 having an amino acid sequence of SEQ ID NO:
- 66, and a CDR3 having an amino acid sequence of SEQ ID NO:
- 68;
- (ii) a light chain FR1 having the amino acid sequence of SEQ ID NO:
- 63 or the amino acid sequence of SEQ ID NO:
- 63 except for one or more substitutions selected from the group consisting of:
- (a) a substitution of aspartic acid (D) by alanine (A) at position 1 utilizing the Kabat numbering system;
- (b) a substitution of valine (V) by glutamine (Q) at position 3 utilizing the Kabat numbering system;
- (c) a substitution of leucine (L) by methionine (M) at position 4 utilizing the Kabat numbering system;
- (d) a substitution of alanine (A) by serine (S) at position 9 utilizing the Kabat numbering system;
- (e) a substitution of alanine (A) by serine (S) at position 12 utilizing the Kabat numbering system;
- (r) a substitution of valine (V) by alanine (A) at position 13 utilizing the Kabat numbering system;
- (g) a substitution of leucine (L) by valine (V) at position 15 utilizing the Kabat numbering system;
- (h) a substitution of glutamine (Q) by aspartic acid (D) at position 17 utilizing the Kabat numbering system;
- (i) a substitution of alanine (A) by valine (V) at position 19 utilizing the Kabat numbering system;
- and
- (j) a substitution of serine (S) by threonine (T) at position 22;
- utilizing the Kabat numbering system;
- and
- (iii) a light chain FR2 having the amino acid sequence of SEQ ID NO:
- 65 or the amino acid sequence of SEQ ID NO:
- 65 except for one or more substitutions selected from the group consisting of:
- (a) a substitution of tyrosine (Y) by phenylalanine (F) at position 40 utilizing the Kabat numbering system;
- (b) a substitution of lysine (K) by arginine (R) at position 43 utilizing the Kabat numbering system;
- (c) a substitution of glutamine (Q) by lysine (K) at position 46 utilizing the Kabat numbering system;
- (d) a substitution of phenylalanine (F) by alanine (A) or serine (S) at position 47 utilizing the Kabat numbering system;
- (e) a substitution of lysine (K) by arginine (R) at position 49 utilizing the Kabat numbering system;
- and
- (f) a substitution of leucine (L) by arginine (R) at position 50 utilizing the Kabat numbering system;
- and
- (iv) a light chain FR3 having the amino acid sequence of SEQ ID NO:
- 67 or the amino acid sequence of SEQ ID NO:
- 67 except for one or more substitutions selected from the group consisting of:
- (a) a substitution of isoleucine (I) by valine (V) at position 62 utilizing the Kabat numbering system;
- (b) a substitution of alanine (A) by serine (S) or proline (P) at position 64 utilizing the Kabat numbering system;
- (c) a substitution of serine (S) by tyrosine (Y) at position 71 utilizing the Kabat numbering system;
- (d) a substitution of arginine (R) by glycine (G) at position 72 utilizing the Kabat numbering system;
- (e) a substitution of aspartic acid (D) by glutamic acid (E) at position 74 utilizing the Kabat numbering system;
- (f) a substitution of leucine (L) by phenylalanine (F) at position 77 utilizing the Kabat numbering system;
- (g) a substitution of asparagine (N) by serine (S) at position 80 utilizing the Kabat numbering system;
- (h) a substitution of proline (P) by asparagine (N) or serine (S) at position 81 utilizing the Kabat numbering system;
- (i) a substitution of valine (V) by leucine (L) or isoleucine (I) at position 82 utilizing the Kabat numbering system;
- (j) a substitution of glutamic acid (E) by glutamine (Q) at position 83 utilizing the Kabat numbering system;
- (k) a substitution of alanine (A) by proline (P) or serine (S) at position 84 utilizing the Kabat numbering system;
- (l) a substitution of aspartic acid (D) glutamic acid (E) at position 85 utilizing the Kabat numbering system;
- (m) a substitution of valine (V) by isoleucine (I), phenylalanine (F) or alanine (A) at position 87;
- utilizing the Kabat numbering system;
- (n) a substitution of threonine (T) by valine (V) or tyrosine (Y) at position 89 utilizing the Kabat numbering system;
- and
- (o) a substitution of tyrosine (Y) by phenylalanine (F) at position 91 utilizing the Kabat numbering system;
- and
- (v) a light chain FR4 having the amino acid sequence of SEQ ID NO:
- 69 or the amino acid sequence of SEQ ID NO:
- 69 except for one or more conservative substitutions therein.
115 more elements
A humanized antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region having an amino acid sequence set forth as SEQ ID NO:
- 43 and a light chain variable region having an amino acid sequence set forth as SEQ ID NO:
- 50.
A humanized antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region having an amino acid sequence set forth as SEQ ID NO:
- 44 and a light chain variable region having an amino acid sequence set forth as SEQ ID NO:
- 54.
A humanized antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region having an amino acid sequence set forth as SEQ ID NO:
- 48 and a light chain variable region having an amino acid sequence set forth as SEQ ID NO:
- 52.
A humanized antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region having an amino acid sequence set forth as SEQ ID NO:
- 45 and a light chain variable region having an amino acid sequence set forth as SEQ ID NO:
- 155.
A humanized antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region having an amino acid sequence set forth as SEQ ID NO:
- 46 and a light chain variable region having an amino acid sequence set forth as SEQ ID NO:
- 51.
A humanized antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region having an amino acid sequence set forth as SEQ ID NO:
- 47 and a light chain variable region having an amino acid sequence set forth as SEQ ID NO:
- 53.
Dependencies are inferred from the claim text.