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US 2016/0355583 A1Published application
Antibodies targeting bone morphogenetic protein 9 (bmp9) and methods therefor
AssigneeNovartis AG
InventorsZijun CHEN, Sujun DENG, Yun HE, Dagang HUANG, Markus KUGLER, Qian LI, Chris Xiangyang LU, Xiao LUO, Yongqiang SHAN, Kathrin Ulrike TISSOT-DAGUETTE, Jing WU
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Abstract
The present invention relates to isolated antibodies and antigen-binding fragments thereof which bind human BMP9 and compositions and methods of use thereof.
Claims58
An isolated antibody or antigen-binding fragment thereof, which binds human BMP9 and comprises:
- (a) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs:
- 61, 62 and 63, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs:
- 71, 72 and 73, respectively;
- (b) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs:
- 64, 65 and 66, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs:
- 74, 75 and 76, respectively;
- (c) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs:
- 1, 2 and 3, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs:
- 11, 12 and 13, respectively;
- (d) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs:
- 4, 5 and 6, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs:
- 14, 15 and 16, respectively;
- (e) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs:
- 21, 22 and 23, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs:
- 31, 32 and 33, respectively;
- (f) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs:
- 24, 25 and 26, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs:
- 34, 35 and 36, respectively;
- (g) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs:
- 41, 42 and 43, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs:
- 51, 52 and 53, respectively;
- (h) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs:
- 44, 45 and 46, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs:
- 54, 55 and 56, respectively;
- (i) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs:
- 81, 82 and 83, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs:
- 91, 92 and 93, respectively;
- (j) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs:
- 84, 85 and 86, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs:
- 94, 95 and 96, respectively;
- (k) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs:
- 101, 102 and 103, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs:
- 111, 112 and 113, respectively;
- (l) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs:
- 104, 105 and 106, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs:
- 114, 115 and 116, respectively;
- (m) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs:
- 121, 122 and 123, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs:
- 131, 132 and 133, respectively;
- (n) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs:
- 124, 125 and 126, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs:
- 134, 135 and 136, respectively;
- (o) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs:
- 141, 142 and 143, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs:
- 151, 152 and 153, respectively;
- (p) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs:
- 144, 145 and 146, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs:
- 154, 155 and 156, respectively;
- (q) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs:
- 161, 162 and 163, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs:
- 171, 172 and 173, respectively;
- or
- (r) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs:
- 164, 165 and 166, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs:
- 174, 175 and 176, respectively.
52 more elements
An isolated antibody or antigen binding fragment thereof which binds human BMP9, (a) which has at least about 1000-fold greater affinity for human BMP9 than for human BMP10, for human BMP7 and for human BMP2;
- and (b) binds to human BMP9, cyno BMP9, rat BMP9 and murine BMP9 with a KD less than 1 nM.
An isolated antibody or antigen-binding fragment thereof, which:
- (a) binds to human BMP9 and inhibits the binding of human BMP9 to a BMP Type I receptor, e.g., ALK1, ALK2 or ALK3;
- (b) binds to human BMP9 and inhibits the binding of human BMP9 to a BMP Type II receptor, e.g., ActIIRB;
- or
- (c) binds to human BMP9 and inhibits the binding of human BMP9 to both a BMP Type I receptor, e.g., ALK1, ALK2 or ALK3, and a BMP Type II receptor, e.g., ActIIRB.
1 more element
An isolated antibody or antigen-binding fragment thereof, which (a) binds to the mature fragment of human BMP9 at an epitope within amino acid residues 21-25, 43-60, 86 and 96 of SEQ ID NO:
- 215;
- or (b) binds to the mature fragment of human BMP9 at an epitope within amino acid residues 83-85 and 95-100 of SEQ ID NO:
- 215.
An isolated antibody or antigen-binding fragment thereof, comprising:
- (a) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs:
- 184, 185 and 186, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs:
- 192, 193 and 194, respectively;
- (b) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs:
- 181, 182 and 183, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs:
- 189, 190 and 191, respectively;
- (c) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs:
- 197, 198, and 199, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs:
- 205, 206, and 207, respectively;
- or
- (d) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs:
- 200, 201, and 202, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs:
- 208, 209, and 210, respectively.
10 more elements
An isolated polynucleotide comprising a nucleic acid sequence encoding a VH or a VL sequence of an antibody or antigen-binding fragment thereof which binds human BMP9, wherein the antibody or antigen-binding fragment thereof comprises:
- (a) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs:
- 61, 62 and 63, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs:
- 71, 72 and 73, respectively;
- (b) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs:
- 64, 65 and 66, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs:
- 74, 75 and 76, respectively;
- (c) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs:
- 1, 2 and 3, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs:
- 11, 12 and 13, respectively;
- (d) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs:
- 4, 5 and 6, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs:
- 14, 15 and 16, respectively;
- (e) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs:
- 21, 22 and 23, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs:
- 31, 32 and 33, respectively;
- (f) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs:
- 24, 25 and 26, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs:
- 34, 35 and 36, respectively;
- (g) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs:
- 41, 42 and 43, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs:
- 51, 52 and 53, respectively;
- (h) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs:
- 44, 45 and 46, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs:
- 54, 55 and 56, respectively;
- (i) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs:
- 81, 82 and 83, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs:
- 91, 92 and 93, respectively;
- (j) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs:
- 84, 85 and 86, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs:
- 94, 95 and 96, respectively;
- (k) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs:
- 101, 102 and 103, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs:
- 111, 112 and 113, respectively;
- (l) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs:
- 104, 105 and 106, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs:
- 114, 115 and 116, respectively;
- (m) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs:
- 121, 122 and 123, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs:
- 131, 132 and 133, respectively;
- (n) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs:
- 124, 125 and 126, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs:
- 134, 135 and 136, respectively;
- (o) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs:
- 141, 142 and 143, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs:
- 151, 152 and 153, respectively;
- (p) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs:
- 144, 145 and 146, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs:
- 154, 155 and 156, respectively;
- (q) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs:
- 161, 162 and 163, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs:
- 171, 172 and 173, respectively;
- or
- (r) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs:
- 164, 165 and 166, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs:
- 174, 175 and 176, respectively.
52 more elements
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Dependencies are inferred from the claim text.