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METHODS OF COMBINED THERAPY WITH APPLICATION OF MOLECULES RELATING TO PSL AND PCRV PSEUDOMONAS

机译:与PSL和PCRV假单胞菌有关的分子联合治疗的方法

摘要

1. An isolated binding molecule or antigen-binding fragment thereof that specifically binds to Pseudomonas PcrV, where the binding molecule: (a) binds to the same Pseudomonas PcrV epitope as the antibody or antigen-binding fragment thereof containing the variable region of the heavy chain ( VH) containing the amino acid sequence of SEQ ID NO: 216 and the variable region of the light chain (VL) containing the amino acid sequence of SEQ ID NO: 217; (b) competitively inhibits the binding of PcrV Pseudomonas to the antibody or its antigen-binding f agmentom containing VH-region, comprising the amino acid sequence of SEQ ID NO: 216 and VL-region, comprising the amino acid sequence of SEQ ID NO: 217; or (c) a combination of (a) and (b). 2. The binding molecule according to claim 1, comprising: (a) a heavy chain CDR1 comprising SYAMN (SEQ ID NO: 218), or a variant thereof, containing 1, 2, 3, or 4 conservative amino acid substitutions; Heavy chain CDR2 containing AITISGITAYYTDSVKG (SEQ ID NO: 219), or a variant thereof, containing 1, 2, 3 or 4 conservative amino acid substitutions; and a heavy chain CDR3 containing EEFLPGTHYYYGMDV (SEQ ID NO: 220), or a variant thereof containing 1, 2, 3 or 4 conservative amino acid substitutions; (b) a light chain CDR1 containing RASQGIRNDLG (SEQ ID NO: 221), or a variant containing 1, 2, 3 or 4 conservative amino acid substitutions; CDR2 light chain containing SASTLQS (SEQ ID NO: 222), or a variant thereof containing 1, 2, 3 or 4 conservative amino acid substitutions; and CDR3 light chain containing LQDYNYPWT (SEQ ID NO: 223), or a variant thereof, containing 1, 2, 3 or 4 conservative amino acid substitutions; or (c) a combination of (a) and (b). 3. A binding molecule according to claim 1, comprising: (a) a variable region of a heavy chain that is at least 90% identical to p
机译:1.一种特异性结合假单胞菌PcrV的分离的结合分子或其抗原结合片段,其中结合分子:(a)与包含重链可变区的抗体或其抗原结合片段的相同假单胞菌PcrV表位结合。含有SEQ ID NO:216的氨基酸序列的链(VH)和含有SEQ ID NO:217的氨基酸序列的轻链的可变区(VL); (b)竞争性抑制PcrV假单胞菌与抗体或其包含抗原结合片段的VH区的结合,所述VH区包含SEQ ID NO:216的氨基酸序列和VL区,其包含SEQ ID NO:2的氨基酸序列:217;或(c)(a)和(b)的组合。 2.根据权利要求1的结合分子,其包含:(a)包含SYAMN(SEQ ID NO:218)或其变体的重链CDR1,其包含1、2、3或4个保守氨基酸取代;和含有AITISGITAYYTDSVKG(SEQ ID NO:219)或其变体的重链CDR2,其含有1、2、3或4个保守氨基酸取代;含有EEFLPGTHYYYGMDV(SEQ ID NO:220)或其含有1、2、3或4个保守氨基酸取代的变体的重链CDR3; (b)含有RASQGIRNDLG(SEQ ID NO:221)或含有1、2、3或4个保守氨基酸取代的变体的轻链CDR1;含有SASTLQS(SEQ ID NO:222)或其包含1、2、3或4个保守氨基酸取代的变体的CDR2轻链;含有LQDYNYPWT(SEQ ID NO:223)或其变体的,具有1、2、3或4个保守氨基酸取代的CDR3轻链;或(c)(a)和(b)的组合。 3.根据权利要求1的结合分子,其包含:(a)与p至少90%相同的重链可变区。

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