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US 11,447,554 B2Granted
Anti-ALK2 antibody
AssigneesSaitama Medical University, Daiichi Sankyo Company, Limited
InventorsTakenobu Katagiri, Kenji Osawa, Sho Tsukamoto, Shinnosuke Tsuji, Yoshirou Kawaguchi, Kensuke Nakamura
Life of this patent
Estimating the term…
Abstract
This application provides: an antibody which specifically binds to an ALK2 protein and has an activity of inhibiting BMP signal transduction mediated by ALK2; a method for producing the antibody; and a pharmaceutical composition comprising the antibody, for treating and/or preventing ectopic ossification and/or bone dysplasia, anemia, or diffuse intrinsic pontine glioma (DIPG).
Claims27
An antibody or an antigen-binding fragment thereof, comprising:
- (i) heavy chain CDRs consisting of the amino acid sequences of SEQ ID NO:
- 65 for CDRH1, SEQ ID NO:
- 66 for CDRH2, and SEQ ID NO:
- 67 for CDRH3;
- and light chain CDRs consisting of the amino acid sequences of SEQ ID NO:
- 68 for CDRL1, SEQ ID NO:
- 69 for CDRL2, and SEQ ID NO:
- 70 for CDRL3;
- (ii) a heavy chain variable region sequence consisting of amino acid numbers 20 to 140 of the amino acid sequence of SEQ ID NO:
- 107;
- and a light chain comprising a light chain variable region sequence consisting of amino acid numbers 21 to 129 of the amino acid sequence of SEQ ID NO:
- 52;
- (iii) a heavy chain comprising the amino acid sequence consisting of amino acid numbers 20 to 470 of the amino acid sequence of SEQ ID NO:
- 107;
- and a light chain comprising the amino acid sequence consisting of amino acid numbers 21 to 234 of the amino acid sequence of SEQ ID NO:
- 52;
- (iv) heavy chain CDRs consisting of the amino acid sequences of SEQ ID NO:
- 72 for CDRH1, SEQ ID NO:
- 73 for CDRH2, and SEQ ID NO:
- 74 for CDRH3;
- and light chain CDRs consisting of the amino acid sequences of SEQ ID NO:
- 75 for CDRL1, SEQ ID NO:
- 76 for CDRL2, and SEQ ID NO:
- 77 for CDRL3;
- (v) a heavy chain variable region sequence consisting of amino acid numbers 20 to 137 of the amino acid sequence of SEQ ID NO:
- 113;
- and a light chain comprising a light chain variable region sequence consisting of amino acid numbers 21 to 128 of the amino acid sequence of SEQ ID NO:
- 119;
- (vi) a heavy chain comprising the amino acid sequence consisting of amino acid numbers 20 to 467 of the amino acid sequence of SEQ ID NO:
- 113;
- and a light chain comprising the amino acid sequence consisting of amino acid numbers 21 to 233 of the amino acid sequence of SEQ ID NO:
- 119;
- (vii) heavy chain CDRs consisting of the amino acid sequences of SEQ ID NO:
- 59 for CDRH1, SEQ ID NO:
- 60 for CDRH2, and SEQ ID NO:
- 61 for CDRH3;
- and light chain CDRs consisting of the amino acid sequences of SEQ ID NO:
- 62 for CDRL1, SEQ ID NO:
- 63 or 71 for CDRL2, and SEQ ID NO:
- 64 for CDRL3;
- (viii) a heavy chain variable region sequence consisting of amino acid numbers 20 to 142 of the amino acid sequence of SEQ ID NO:
- 105;
- and a light chain comprising a light chain variable region sequence consisting of amino acid numbers 21 to 133 of the amino acid sequence of SEQ ID NO:
- 36;
- (ix) a heavy chain comprising the amino acid sequence consisting of amino acid numbers 20 to 468 of the amino acid sequence of SEQ ID NO:
- 105;
- and a light chain comprising the amino acid sequence consisting of amino acid numbers 21 to 238 of the amino acid sequence of SEQ ID NO:
- 36;
- (x) heavy chain CDRs consisting of the amino acid sequences of SEQ ID NO:
- 78 for CDRH1, SEQ ID NO:
- 79 for CDRH2, and SEQ ID NO:
- 80 for CDRH3;
- and light chain CDRs consisting of the amino acid sequences of SEQ ID NO:
- 81 for CDRL1, SEQ ID NO:
- 82 for CDRL2, and SEQ ID NO:
- 83 for CDRL3;
- (xi) a heavy chain variable region sequence consisting of amino acid numbers 20 to 137 of the amino acid sequence of SEQ ID NO:
- 123;
- and a light chain comprising a light chain variable region sequence consisting of amino acid numbers 21 to 129 of the amino acid sequence of SEQ ID NO:
- 129;
- or
- (xii) a heavy chain comprising the amino acid sequence consisting of amino acid numbers 20 to 467 of the amino acid sequence of SEQ ID NO:
- 123;
- and a light chain comprising the amino acid sequence consisting of amino acid numbers 21 to 234 of the amino acid sequence of SEQ ID NO:
- 129.
62 more elements
An antibody or an antigen binding fragment thereof, wherein the antibody comprises:
- (a) a heavy chain comprising amino acids 20 to 142 of SEQ ID NO:
- 28 and a light chain comprising amino acids 21 to 133 of SEQ ID NO:
- 32;
- (b) a heavy chain comprising amino acids 20 to 142 of SEQ ID NO:
- 28 and a light chain comprising amino acids 21 to 133 of SEQ ID NO:
- 34;
- (c) a heavy chain comprising 20 to 142 of SEQ ID NO:
- 30 and a light chain comprising amino acids 21 to 133 of SEQ ID NO:
- 32;
- (d) a heavy chain comprising 20 to 142 of SEQ ID NO:
- 30 and a light chain comprising amino acids 21 to 133 of SEQ ID NO:
- 34;
- (e) a heavy chain comprising 20 to 142 of SEQ ID NO:
- 30 and a light chain comprising amino acids 21 to 133 of SEQ ID NO:
- 36;
- (f) a heavy chain comprising 20 to 142 of SEQ ID NO:
- 30 and a light chain comprising amino acids 21 to 133 of SEQ ID NO:
- 38;
- (g) a heavy chain comprising amino acids 20 to 142 of SEQ ID NO:
- 105 and a light chain comprising amino acids 21 to 133 of SEQ ID NO:
- 36;
- (h) a heavy chain comprising amino acids 20 to 140 of SEQ ID NO:
- 40 and a light chain comprising amino acids 21 to 129 of SEQ ID NO:
- 50;
- (i) a heavy chain comprising amino acids 20 to 140 of SEQ ID NO:
- 40 and a light chain comprising amino acids 21 to 129 of SEQ ID NO:
- 52;
- (j) a heavy chain comprising amino acids 20 to 140 of SEQ ID NO:
- 40 and a light chain comprising amino acids 21 to 129 of SEQ ID NO:
- 54;
- (k) a heavy chain comprising amino acids 20 to 140 of SEQ ID NO:
- 42 and a light chain comprising amino acids 21 to 129 of SEQ ID NO:
- 50;
- (l) a heavy chain comprising amino acids 20 to 140 of SEQ ID NO:
- 42 and a light chain comprising amino acids 21 to 129 of SEQ ID NO:
- 52;
- (m) a heavy chain comprising amino acids 20 to 140 of SEQ ID NO:
- 42 and a light chain comprising amino acids 21 to 129 of SEQ ID NO:
- 54;
- (n) a heavy chain comprising amino acids 20 to 140 of SEQ ID NO:
- 44 and a light chain comprising amino acids 21 to 129 of SEQ ID NO:
- 50;
- (o) a heavy chain comprising amino acids 20 to 140 of SEQ ID NO:
- 44 and a light chain comprising amino acids 21 to 129 of SEQ ID NO:
- 52;
- (p) a heavy chain comprising amino acids 20 to 140 of SEQ ID NO:
- 44 and a light chain comprising amino acids 21 to 129 of SEQ ID NO:
- 54;
- (q) a heavy chain comprising amino acids 20 to 140 of SEQ ID NO:
- 44 and a light chain comprising amino acids 21 to 129 of SEQ ID NO:
- 56;
- (r) a heavy chain comprising amino acids 20 to 140 of SEQ ID NO:
- 46 and a light chain comprising amino acids 21 to 129 of SEQ ID NO:
- 54;
- (s) a heavy chain comprising amino acids 20 to 140 of SEQ ID NO:
- 46 and a light chain comprising amino acids 21 to 129 of SEQ ID NO:
- 56;
- (t) a heavy chain comprising amino acids 20 to 140 of SEQ ID NO:
- 46 and a light chain comprising amino acids 21 to 129 of SEQ ID NO:
- 58;
- (u) a heavy chain comprising amino acids 20 to 140 of SEQ ID NO:
- 48 and a light chain comprising amino acids 21 to 129 of SEQ ID NO:
- 56;
- (v) a heavy chain comprising amino acids 20 to 140 of SEQ ID NO:
- 107 and a light chain comprising amino acids 21 to 129 of SEQ ID NO:
- 52;
- (w) a heavy chain comprising amino acids 20 to 140 of SEQ ID NO:
- 109 and a light chain comprising amino acids 21 to 129 of SEQ ID NO:
- 56;
- (x) a heavy chain comprising amino acids 20 to 137 of SEQ ID NO:
- 111 and a light chain comprising amino acids 21 to 128 of SEQ ID NO:
- 115;
- (y) a heavy chain comprising amino acids 20 to 137 of SEQ ID NO:
- 111 and a light chain comprising amino acids 21 to 128 of SEQ ID NO:
- 117;
- (z) a heavy chain comprising amino acids 20 to 137 of SEQ ID NO:
- 111 and a light chain comprising amino acids 21 to 128 of SEQ ID NO:
- 119;
- (aa) a heavy chain comprising amino acids 20 to 137 of SEQ ID NO:
- 113 and a light chain comprising amino acids 21 to 128 of SEQ ID NO:
- 115;
- (bb) a heavy chain comprising amino acids 20 to 137 of SEQ ID NO:
- 113 and a light chain comprising amino acids 21 to 128 of SEQ ID NO:
- 117);
- (cc) a heavy chain comprising amino acids 20 to 137 of SEQ ID NO:
- 113 and a light chain comprising amino acids 21 to 128 of SEQ ID NO:
- 119;
- (dd) a heavy chain comprising amino acids 20 to 137 of SEQ ID NO:
- 121 and a light chain comprising amino acids 21 to 129 of SEQ ID NO:
- 125;
- (ee) a heavy chain comprising amino acids 20 to 137 of SEQ ID NO:
- 121 and a light chain comprising amino acids 21 to 129 of SEQ ID NO:
- 127;
- (ff) a heavy chain comprising amino acids 20 to 137 of SEQ ID NO:
- 121 and a light chain comprising amino acids 21 to 129 of SEQ ID NO:
- 129;
- (gg) a heavy chain comprising amino acids 20 to 137 of SEQ ID NO:
- 123 and a light chain comprising amino acids 21 to 129 of SEQ ID NO:
- 125;
- (hh) a heavy chain comprising amino acids 20 to 137 of SEQ ID NO:
- 123 and a light chain comprising amino acids 21 to 129 of SEQ ID NO:
- 127;
- or
- (ii) a heavy chain comprising amino acids 20 to 137 of SEQ ID NO:
- 123 and a light chain comprising amino acids 21 to 129 of SEQ ID NO:
- 129.
103 more elements
Dependencies are inferred from the claim text.