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US 8,802,096 B2Granted
Anti-C5a binding antibodies with high block activity
AssigneeInflaRx GmbH
InventorsRenfeng Guo, Niels Christoph Riedemann, Yan Li, Beifen Shen
Life of this patent
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Abstract
The present invention relates to binding moieties that specifically bind to a conformational epitope of C5a, in particular human C5a. Preferred binding moieties are anti-C5a antibodies that bind to this conformational epitope. The binding moieties described herein are useful as active agents in pharmaceutical compositions for the treatment and prevention of various acute and chronic diseases, in particular acute inflammatory diseases, such as the systemic inflammatory response syndrome (SIRS), and different degrees of sepsis including sepsis, severe sepsis, and septic shock.
Claims15
A binding moiety which binds to a conformational epitope formed by amino acid sequences NDETCEQRA (SEQ ID NO:
- 2) and SHKDMQL (SEQ ID NO:
- 3) of C5a, wherein the binding moiety binds to at least one amino acid within the amino acid sequence according to SEQ ID NO:
- 2 and to at least one amino acid within the amino acid sequence according to SEQ ID NO:
- 3;
- wherein said binding moiety has a binding constant to C5a with a Kd value of 100 nM or less;
- and wherein said binding moiety is an antibody or an antigen-binding fragment thereof.
3 more elements
An antibody or an antigen-binding fragment thereof comprising:
- (i) a heavy chain CDR3 sequence as set forth in SEQ ID NO:
- 6;
- or
- (ii) a heavy chain CDR3 sequence as set forth in SEQ ID NO:
- 7;
- and further comprising at least one of the following sequences:
- (iii) a heavy chain CDR2 sequence according to SEQ ID NO:
- 10;
- (iv) a heavy chain CDR2 sequence according to SEQ ID NO:
- 11;
- (v) a light chain CDR2 sequence according to SEQ ID NO:
- 12;
- (vi) a light chain CDR2 sequence according to SEQ ID NO:
- 13;
- (vii) a heavy chain CDR1 sequence according to SEQ ID NO:
- 14;
- (viii) a heavy chain CDR1 sequence according to SEQ ID NO:
- 15;
- (ix) a light chain CDR1 sequence according to SEQ ID NO:
- 16;
- or
- (x) a light chain CDR1 sequence according to SEQ ID NO:
- 17;
- wherein the antibody or antigen-binding fragment thereof binds to a conformational epitope formed by amino acid sequences NDETCEQRA (SEQ ID NO:
- 2) and SHKDMQL (SEQ ID NO:
- 3) of C5a,
- wherein the antibody or antigen-binding fragment thereof binds to at least one amino acid within the amino acid sequence according to SEQ ID NO:
- 2 and to at least one amino acid within the amino acid sequence according to SEQ ID NO:
- 3;
- and
- wherein said antibody or antigen-binding fragment thereof has a binding constant to C5a with a Kd value of 100 nM or less.
28 more elements
An antibody or an antigen-binding fragment thereof comprising:
- (i) a light chain CDR3 sequence as set forth in SEQ ID NO:
- 8;
- or
- (ii) a light chain CDR3 sequence as set forth in SEQ ID NO:
- 9;
- wherein the antibody or antigen-binding fragment thereof binds to a conformational epitope formed by amino acid sequences NDETCEQRA (SEQ ID NO:
- 2) and SHKDMQL (SEQ ID NO:
- 3) of C5a;
- wherein the antibody or antigen-binding fragment thereof binds to at least one amino acid within the amino acid sequence according to SEQ ID NO:
- 2 and to at least one amino acid within the amino acid sequence according to SEQ ID NO:
- 3;
- and
- wherein said antibody or antigen binding fragment thereof has a binding constant to C5a with a Kd value of 100 nM or less.
10 more elements
An antibody or an antigen-binding fragment thereof comprising a set of heavy chain CDR3, heavy chain CDR2, and heavy chain CDR1 sequences selected from one of the following sets:
- a heavy chain CDR3 sequence according to SEQ ID NO:
- 6, a heavy chain CDR2 sequence according to SEQ ID NO:
- 10, and a heavy chain CDR1 sequence according to SEQ ID NO:
- 14;
- (ii) a heavy chain CDR3 sequence according to SEQ ID NO:
- 6, a heavy chain CDR2 sequence according to SEQ ID NO:
- 10, and a heavy chain CDR1 sequence according to SEQ ID NO:
- 15;
- (iii) a heavy chain CDR3 sequence according to SEQ ID NO:
- 6, a heavy chain CDR2 sequence according to SEQ ID NO:
- 11, and a heavy chain CDR1 sequence according to SEQ ID NO:
- 14;
- (iv) a heavy chain CDR3 sequence according to SEQ ID NO:
- 6, a heavy chain CDR2 sequence according to SEQ ID NO:
- 11, and a heavy chain CDR1 sequence according to SEQ ID NO:
- 15;
- (v) a heavy chain CDR3 sequence according to SEQ ID NO:
- 7, a heavy chain CDR2 sequence according to SEQ ID NO:
- 10, and a heavy chain CDR1 sequence according to SEQ ID NO:
- 14;
- (vi) a heavy chain CDR3 sequence according to SEQ ID NO:
- 7, a heavy chain CDR2 sequence according to SEQ ID NO:
- 10, and a heavy chain CDR1 sequence according to SEQ ID NO:
- 15;
- (vii) a heavy chain CDR3 sequence according to SEQ ID NO:
- 7, a heavy chain CDR2 sequence according to SEQ ID NO:
- 11, and a heavy chain CDR1 sequence according to SEQ ID NO:
- 14;
- and
- (viii) a heavy chain CDR3 sequence according to SEQ ID NO:
- 7, a heavy chain CDR2 sequence according to SEQ ID NO:
- 11, and a heavy chain CDR1 sequence according to SEQ ID NO:
- 15;
- wherein the antibody or antigen-binding fragment thereof binds to a conformational epitope formed by amino acid sequences NDETCEQRA (SEQ ID NO:
- 2) and SHKDMQL (SEQ ID NO:
- 3) of C5a;
- wherein the antibody or antigen-binding fragment thereof binds to at least one amino acid within the amino acid sequence according to SEQ ID NO:
- 2 and to at least one amino acid within the amino acid sequence according to SEQ ID NO:
- 3;
- and
- wherein said antibody or antigen binding fragment thereof has a binding constant to C5a with a Kd value of 100 nM or less.
38 more elements
An antibody or an antigen-binding fragment thereof comprising a set of light chain CDR3, light chain CDR2, and light chain CDR1 sequences selected from one of the following sets:
- (i) a light chain CDR3 sequence according to SEQ ID NO:
- 8, a light chain CDR2 sequence according to SEQ ID NO:
- 12, and a light chain CDR1 sequence according to SEQ ID NO:
- 16;
- (ii) a light chain CDR3 sequence according to SEQ ID NO:
- 8, a light chain CDR2 sequence according to SEQ ID NO:
- 12, and a light chain CDR1 sequence according to SEQ ID NO:
- 17;
- (iii) a light chain CDR3 sequence according to SEQ ID NO:
- 9, a light chain CDR2 sequence according to SEQ ID NO:
- 12, and a light chain CDR1 sequence according to SEQ ID NO:
- 16;
- and
- (iv) a light chain CDR3 sequence according to SEQ ID NO:
- 9, a light chain CDR2 sequence according to SEQ ID NO:
- 12, and a light chain CDR1 sequence according to SEQ ID NO:
- 17;
- wherein the antibody or antigen-binding fragment thereof binds to a conformational epitope formed by amino acid sequences NDETCEQRA (SEQ ID NO:
- 2) and SHKDMQL (SEQ ID NO:
- 3) of C5a;
- wherein the antibody or antigen-binding fragment thereof binds to at least one amino acid within the amino acid sequence according to SEQ ID NO:
- 2 and to at least one amino acid within the amino acid sequence according to SEQ ID NO:
- 3;
- and
- wherein said antibody or antigen binding fragment thereof has a binding constant to C5a with a Kd value of 100 nM or less.
22 more elements
A pharmaceutical composition comprising an antibody or an antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof comprises:
- (i) a heavy chain CDR3 sequence as set forth in SEQ ID NO:
- 6;
- or
- (ii) a heavy chain CDR3 sequence as set forth in SEQ ID NO:
- 7;
- or
- (iii) a light chain CDR3 sequence as set forth in SEQ ID NO:
- 8;
- or
- (iv) a light chain CDR3 sequence as set forth in SEQ ID NO:
- 9;
- wherein the antibody or antigen-binding fragment thereof binds to a conformational epitope formed by amino acid sequences NDETCEQRA (SEQ ID NO:
- 2) and SHKDMQL (SEQ ID NO:
- 3) of C5a;
- wherein the antibody or antigen-binding fragment thereof binds to at least one amino acid within the amino acid sequence according to SEQ ID NO:
- 2 and to at least one amino acid within the amino acid sequence according to SEQ ID NO:
- 3;
- and
- wherein said antibody or antigen binding fragment thereof has a binding constant to C5a with a Kd value of 100 nM or less.
16 more elements
Dependencies are inferred from the claim text.