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US 12,570,728 B2Granted
Combinations of antibodies and bispecific antibodies comprising antigen-binding specifically recognizing Pseudomonas PcrV and Psl
AssigneeBeijing Solobio Genetechnology Company Ltd.
InventorsZhong Li, Maorong Yu
Life of this patent
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Abstract
Provided are bispecific antibodies that specifically recognize PcrV and/or Psl from Pseudomonas aeruginosa, pharmaceutical compositions comprising antibodies specifically recognizing non-overlapping epitopes of Pseudomonas PcrV and/or Psl. Also provided are methods of making and using these antibodies.
Claims13
A bispecific molecule comprising a first antigen-binding domain specifically recognizing Pseudomonas PcrV, and a second antigen-binding domain specifically recognizing Pseudomonas Psl, wherein the first antigen-binding domain comprises:
- (a) a heavy chain variable domain (VH) comprising a heavy chain complementarity determining region (HC-CDR) 1 comprising DX1X2MS (SEQ ID NO:
- 20), wherein X1 is N or Y, and X2 is Y, H or P;
- an HC-CDR2 comprising X1ISESGGSTNYADSVKG (SEQ ID NO:
- 15), wherein X1 is V or G;
- and an HC-CDR3 comprising GRFSTX1SX2HFX3RAVYGMDV (SEQ ID NO:
- 21), wherein X1 is L, S, N or D, X2 is S or A, X3 is F or Y;
- and a light chain variable domain (VL) comprising a light chain complementarity determining region (LC-CDR) 1 comprising RASQGISSYLA (SEQ ID NO:
- 10);
- an LC-CDR2 comprising AASTLQS (SEQ ID NO:
- 11), and an LC-CDR3 comprising QQLSSYPLX1 (SEQ ID NO:
- 19), wherein X1 is S or T;
- or
- (b) a VH comprising a HC-CDR1 comprising SYWMH (SEQ ID NO:
- 22);
- an HC-CDR2 comprising RINEX1EX2SISYADSVKG (SEQ ID NO:
- 44), wherein X1 is D or N, and X2 is T, G or R;
- and an HC-CDR3 comprising DGPYDX1X2DI (SEQ ID NO:
- 45), wherein X1 is S, A, or T, and X2 is F or L;
- and a VL comprising an LC-CDR1 comprising RASQX1VX2X3NLA (SEQ ID NO:
- 46), wherein X1 is S, G or N, X2 is S, R or K and X3 is S or N;
- an LC-CDR2 comprising X1ASSRAT (SEQ ID NO:
- 42), wherein X1 is D or H, and an LC-CDR3 comprising QQYGX1X2PX3T (SEQ ID NO:
- 47), wherein X1 is S, L or N, X2 is S, Q or E and X3 is L or I;
- or wherein the first antigen-binding domain comprises:
- (i) a VH comprising an HC-CDR1 comprising the amino acid sequence SEQ ID NO:
- 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO:
- 4, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO:
- 6;
- and a VL comprising:
- an LC-CDR1 comprising the amino acid sequence of SEQ ID NO:
- 10, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO:
- 11, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO:
- 12;
- or
- (ii) a VH comprising an HC-CDR1 comprising the amino acid sequence SEQ ID NO:
- 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO:
- 5, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO:
- 7;
- and a VL comprising:
- an LC-CDR1 comprising the amino acid sequence of SEQ ID NO:
- 10, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO:
- 11, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO:
- 13;
- or
- (iii) a VH comprising an HC-CDR1 comprising the amino acid sequence SEQ ID NO:
- 22, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO:
- 23, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO:
- 26;
- and a VL comprising:
- an LC-CDR1 comprising the amino acid sequence of SEQ ID NO:
- 30, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO:
- 33, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO:
- 35;
- or
- (iv) a VH comprising an HC-CDR1 comprising the amino acid sequence SEQ ID NO:
- 22, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO:
- 24, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO:
- 27;
- and a VL comprising:
- an LC-CDR1 comprising the amino acid sequence of SEQ ID NO:
- 31, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO:
- 34, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO:
- 36;
- and
- wherein the second antigen-binding domain comprises:
- (a) a VH comprising a HC-CDR1 comprising SSGDYWG (SEQ ID NO:
- 48);
- an HC-CDR2 comprising SIHNX1GSTYYNPSLKG (SEQ ID NO:
- 81), wherein X1 is S or Q;
- and an HC-CDR3 comprising QFGSETYYX1GIX2P (SEQ ID NO:
- 82), wherein X1 is T, N or P, and X2 is D or Q;
- and a VL comprising an LC-CDR1 comprising RSSQSLLHSX1GYNYLD (SEQ ID NO:
- 83), wherein X1 is N or R;
- an LC-CDR2 comprising LGSNRAS (SEQ ID NO:
- 70), and an LC-CDR3 comprising MQALQTPYT (SEQ ID NO:
- 74);
- or
- (b) a VH comprising an HC-CDR1 comprising IHSVH (SEQ ID NO:
- 50);
- an HC-CDR2 comprising TIISSGTTTTYAQSFQD (SEQ ID NO:
- 55);
- and an HC-CDR3 comprising DGX1S (SEQ ID NO:
- 84), wherein X1 is D or T;
- and a VL comprising an LC-CDR1 comprising RASQGISSWLA (SEQ ID NO:
- 68);
- an LC-CDR2 comprising HASTLES (SEQ ID NO:
- 72), and an LC-CDR3 comprising LQAX1SLPHT (SEQ ID NO:
- 85), wherein X1 is N, F, S or K;
- or
- (c) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO:
- 49, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO:
- 54, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO:
- 61;
- and a VL comprising:
- an LC-CDR1 comprising the amino acid sequence of SEQ ID NO:
- 67, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO:
- 71, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO:
- 75;
- or
- (d) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO:
- 51, an HC-CDR2 comprising the amino acid sequence of SEQ ID NOs 56, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO:
- 64;
- and a VL comprising:
- an LC-CDR1 comprising the amino acid sequence of SEQ ID NO:
- 69, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO:
- 73, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO:
- 80;
- or wherein the second antigen-binding domain comprises:
- (i) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO:
- 48, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO:
- 52, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO:
- 57;
- and a VL comprising:
- an LC-CDR1 comprising the amino acid sequence of SEQ ID NO:
- 65, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO:
- 70, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO:
- 74;
- or
- (ii) a VH comprising an HC-CDR1 comprising the amino acid sequence of SEQ ID NO:
- 50, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO:
- 55, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO:
- 62;
- and a VL comprising:
- an LC-CDR1 comprising the amino acid sequence of SEQ ID NO:
- 68, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO:
- 72, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO:
- 76.
124 more elements
Dependencies are inferred from the claim text.