Methods of treating inflammatory disease with anti-IL-8 antibody fragment-polymer conjugates
First Claim
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1. A method of treating an inflammatory disorder in a mammal comprising administering to the mammal an effective amount of a conjugate of a single antibody fragment covalently attached to 1 or 2 polyethylene glycol (PEG) molecules, wherein the antibody fragment is a F(ab′
- )2 comprising (1) a first chain that is either a light chain or a heavy chain (2) a first opposite chain that is either a heavy chain opposite the first light chain or a light chain opposite the first heavy chain (3) a second chain that is either a light chain or a heavy chain and (4) a second opposite chain that is either a heavy chain opposite the second light chain or a light chain opposite the second heavy chair, wherein every PEG molecule is covalently attached to a first cysteine residue in the first or second chain that would ordinarily form a disulfide bridge with a second cysteine residue in the first or second opposite chain, wherein the disulfide bridge is avoided by substitution of another amino acid residue for the second cysteine residue in the first or second opposite chain, wherein the F(ab′
)2 comprises an antigen binding site that binds to human interleukin-8 (IL-8), and wherein the apparent size of the conjugate is at least about 500 kD.
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Abstract
Provided are methods for treating inflammatory diseases in a patient comprising administering to the patient an effective amount of a conjugate consisting essentially of one or more antibody fragments covalently attached to one or more nonproteinaceous polymer molecules, wherein at least one antibody fragment comprises an antigen binding site that binds to human IL-8, and wherein the apparent size of the conjugate is at least about 500 kD.
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Citations
34 Claims
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1. A method of treating an inflammatory disorder in a mammal comprising administering to the mammal an effective amount of a conjugate of a single antibody fragment covalently attached to 1 or 2 polyethylene glycol (PEG) molecules, wherein the antibody fragment is a F(ab′
- )2 comprising (1) a first chain that is either a light chain or a heavy chain (2) a first opposite chain that is either a heavy chain opposite the first light chain or a light chain opposite the first heavy chain (3) a second chain that is either a light chain or a heavy chain and (4) a second opposite chain that is either a heavy chain opposite the second light chain or a light chain opposite the second heavy chair, wherein every PEG molecule is covalently attached to a first cysteine residue in the first or second chain that would ordinarily form a disulfide bridge with a second cysteine residue in the first or second opposite chain, wherein the disulfide bridge is avoided by substitution of another amino acid residue for the second cysteine residue in the first or second opposite chain, wherein the F(ab′
)2 comprises an antigen binding site that binds to human interleukin-8 (IL-8), and wherein the apparent size of the conjugate is at least about 500 kD. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18)
- )2 comprising (1) a first chain that is either a light chain or a heavy chain (2) a first opposite chain that is either a heavy chain opposite the first light chain or a light chain opposite the first heavy chain (3) a second chain that is either a light chain or a heavy chain and (4) a second opposite chain that is either a heavy chain opposite the second light chain or a light chain opposite the second heavy chair, wherein every PEG molecule is covalently attached to a first cysteine residue in the first or second chain that would ordinarily form a disulfide bridge with a second cysteine residue in the first or second opposite chain, wherein the disulfide bridge is avoided by substitution of another amino acid residue for the second cysteine residue in the first or second opposite chain, wherein the F(ab′
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19. A method of treating an inflammatory disorder in a mammal comprising administering to the mammal an effective amount of a conjugate of a single antibody fragment covalently attached to a single polyethylene glycol (PEG) molecule, wherein the antibody fragment is a F(ab′
- )2 comprising (1) a first chain that is either a light chain or a heavy chain (2) a first opposite chain that is either a heavy chain opposite the first light chain or a light chain opposite the first heavy chain (3) a second chain that is either a light chain or a heavy chain and (4) a second opposite chain that is either a heavy chain opposite the second light chain or a light chain opposite the second heavy chain, wherein every PEG molecule is covalently attached to a first cysteine residue in the first or second chain that would ordinarily form a disulfide bridge with a second cysteine residue in the first or second opposite chain, wherein the disulfide bridge is avoided by substitution of another amino acid residue for the second cysteine residue in the first or second opposite chain, wherein the F(ab′
)2 comprises an antigen binding site that binds to human interleukin-8 (IL-8), and wherein the apparent size of the conjugate is at least about 500 kD. - View Dependent Claims (20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34)
- )2 comprising (1) a first chain that is either a light chain or a heavy chain (2) a first opposite chain that is either a heavy chain opposite the first light chain or a light chain opposite the first heavy chain (3) a second chain that is either a light chain or a heavy chain and (4) a second opposite chain that is either a heavy chain opposite the second light chain or a light chain opposite the second heavy chain, wherein every PEG molecule is covalently attached to a first cysteine residue in the first or second chain that would ordinarily form a disulfide bridge with a second cysteine residue in the first or second opposite chain, wherein the disulfide bridge is avoided by substitution of another amino acid residue for the second cysteine residue in the first or second opposite chain, wherein the F(ab′
Specification