Antibody fragment-polymer conjugates and humanized anti-IL-8 monoclonal antibodies
First Claim
1. A conjugate consisting essentially of an antibody fragment covalently modified by one or two nonproteinaceous polymer molecules at a free sulfhydryl group of a cysteine residue within the hinge region of the antibody fragment, wherein (a) the apparent molecular weight of the conjugate, as determined by size exclusion chromatography, is at least about 500 kD, (b) the average actual molecular weight of each nonproteinaceous molecule is at least 20 kD, and (c) the antibody fragment has an antigen binding site that binds human interleukin-8 (IL-8) comprising an anti-IL-8 monoclonal antibody light chain sequence comprising amino acids 1-219 of the humanized antibody light chain 6G4.2.5v11 (SEQ ID NO:
- 51).
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Accused Products
Abstract
Humanized anti-IL-8 monoclonal antibodies and variants thereof are described for use in diagnostic applications and in the treatment of inflammatory disorders. Also described is a conjugate formed by an antibody fragment covalently attached to a non-proteinaceous polymer, wherein the apparent size of the conjugate is at least about 500 kD. The conjugate exhibits substantially improved half-life, mean residence time, and/or clearance rate in circulation as compared to the underivatized parental antibody fragment.
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Citations
10 Claims
- 1. A conjugate consisting essentially of an antibody fragment covalently modified by one or two nonproteinaceous polymer molecules at a free sulfhydryl group of a cysteine residue within the hinge region of the antibody fragment, wherein (a) the apparent molecular weight of the conjugate, as determined by size exclusion chromatography, is at least about 500 kD, (b) the average actual molecular weight of each nonproteinaceous molecule is at least 20 kD, and (c) the antibody fragment has an antigen binding site that binds human interleukin-8 (IL-8) comprising an anti-IL-8 monoclonal antibody light chain sequence comprising amino acids 1-219 of the humanized antibody light chain 6G4.2.5v11 (SEQ ID NO:
- 5. A conjugate consisting essentially of an antibody fragment covalently modified by one or two nonproteinaceous polymer molecules at a free sulfhydryl group of a cysteine residue within the hinge region of the antibody fragment, wherein (a) the apparent molecular weight of the conjugate, as determined by size exclusion chromatography, is at least about 500 kD, (b) the average actual molecular weight of each nonproteinaceous molecule is at least 20 kD, and (c) the antibody fragment has an antigen binding site that binds human interleukin-8 (IL-8) comprising an anti-IL-8 monoclonal antibody heavy chain sequence comprising amino acids 1-230 of the humanized antibody 6G4.2.5v11 heavy chain (SEQ ID NO:
Specification