Methods of use of antibodies with reduced immunogenicity or toxicity
Humanized antibodies which bind the NR-LU-13 antigen, conjugates containing such antibodies, and their use in pretargeting methods and conventional antibody therapy and immunodiagnosis are provided.
1 - 50 . (canceled)
51 . A method for treating a patient in need thereof with a therapeutic antibody or antigen-binding fragment thereof, comprising administering to said patient in an amount effective for treatment a therapeutic antibody or an antigen-binding fragment thereof, wherein said antibody or said antibody fragment either does not possess N-linked glycosylation or its N-linked glycosylation has been modified post expression to reduce immunogenicity or toxicity.
52 . The method of claim 51 wherein said antibody or said antibody fragment is humanized.
53 . The method of claim 51 wherein said antibody or said antibody fragment does not possess O-linked glycosylation.
54 . The method of claim 51 wherein the nucleic acids encoding said antibody or said antibody fragment have been mutated to prevent N-linked glycosylation.
55 . The method of claim 51 wherein the N-linked glycosylation of said antibody or said antibody fragment has been modified chemically.
56 . The method of any one of claims 51 - 55 wherein an active agent is conjugated to said antibody or said antibody fragment.
57 . A therapeutic, humanized antibody or an antigen-binding fragment thereof, wherein said antibody or said antibody fragment either does not possess N-linked glycosylation or its N-linked glycosylation has been modified post expression to reduce immunogenicity or toxicity.
58 . The antibody or antibody fragment of claim 57 wherein said antibody or said antibody fragment does not possess O-linked glycosylation.
59 . The antibody or antibody fragment of claim 57 wherein the polynucleotides encoding said antibody fragment have been substituted or deleted to prevent N-linked glycosylation.
60 . The antibody or antibody fragment of claim 57 wherein the N-linked glycosylation has been chemically modified post expression.
61 . The antibody or antibody fragment of any one of claims 57 - 60 wherein an active agent is conjugated to said antibody or said antibody fragment.
62 . A method of preparing a therapeutic, humanized antibody, or an antigen-binding fragment thereof, with reduced immunogenicity or toxicity, comprising the steps of:
(a) selecting an expression system for the characteristic that said system does not N-link glycosylate an antibody or an antibody fragment; and
(b) expressing in said expression system a nucleotide sequence comprising nucleic acids encoding a therapeutic, humanized antibody or an antigen-binding fragment thereof.
63 . A method of preparing a therapeutic, humanized antibody, or an antigen-binding fragment thereof, without N-linked glycosylation to reduce immunogenicity or toxicity, comprising expressing in an expression system a nucleotide sequence comprising nucleic acids encoding a therapeutic, humanized antibody or antigen-binding fragment thereof, wherein said expression system does not N-link glycosylate said antibody or said antibody fragment.
64 . The method of claim 62 or 63 wherein said antibody or said antibody fragment does not possess O-linked glycosylation.
65 . The method of claim 62 or 63 wherein an active agent is conjugated to said antibody or said antibody fragment.
66 . A method for imaging target cells in an individual, comprising the steps of:
(a) administering to an individual in an amount effective for imaging, an antibody specific for target cells or an antigen-binding fragment thereof, wherein said antibody or said antibody fragment either does not possess N-linked glycosylation or its N-linked glycosylation has been modified post expression to reduce immunogenicity or toxicity; and
(b) detecting said antibody or said antibody fragment, thereby imaging target cells in said individual.
67 . The method of claim 66 wherein said antibody or said antibody fragment is humanized.
68 . The method of claim 66 wherein said antibody or said antibody fragment does not possess O-linked glycosylation.
69 . The method of claim 66 wherein the nucleic acids encoding said antibody or said antibody fragment have been mutated to prevent N-linked glycosylation.
70 . The method of claim 66 wherein the N-linked glycosylation of said antibody or said antibody fragment has been modified chemically.
71 . The method of any one of claims 66 - 70 wherein an imaging agent is conjugated to said antibody or said antibody fragment.
72 . The method of claim 71 wherein the imaging agent is a radionuclide.
73 . The method of claim 72 wherein the radionuclide is 99m Tc, 111 In or 18 F.
74 . A humanized antibody that is useful for imaging target cells or an antigen-binding fragment thereof, wherein said antibody or said antibody fragment either does not possess N-linked glycosylation or its N-linked glycosylation has been modified post expression to reduce immunogenicity or toxicity, and said antibody or said antibody fragment is useful for imaging target cells.
75 . The antibody or antibody fragment of claim 74 wherein said antibody or said antibody fragment does not possess O-linked glycosylation.
76 . The antibody or antibody fragment of claim 74 wherein the polynucleotides encoding said antibody fragment have been substituted or deleted to prevent N-linked glycosylation.
77 . The antibody or antibody fragment of claim 74 wherein the N-linked glycosylation has been chemically modified post expression.
78 . The antibody or antibody fragment of any one of claims 74 - 77 wherein an imaging agent is conjugated to said antibody or said antibody fragment.
79 . The antibody or antibody fragment of claim 78 wherein the imaging agent is a radionuclide.
80 . The antibody or antibody fragment of claim 79 wherein the radionuclide is 99m Tc, 111 In or 18 F.
81 . A method of preparing a humanized antibody, or an antigen-binding fragment thereof, with reduced immunogenicity or toxicity and useful for imaging target cells, comprising the steps of:
(a) selecting an expression system for the characteristic that said system does not N-link glycosylate an antibody or an antibody fragment; and
(b) expressing in said expression system a nucleotide sequence comprising nucleic acids encoding a humanized antibody, or an antigen-binding fragment thereof, that is useful for imaging target cells.
82 . A method of preparing a humanized antibody, or an antigen-binding fragment thereof, without N-linked glycosylation to reduce immunogenicity or toxicity and said antibody or said antibody fragment is useful for imaging target cells, comprising expressing in an expression system a nucleotide sequence comprising nucleic acids encoding a humanized antibody or antigen-binding fragment thereof that is useful for imaging target cells, wherein said expression system does not N-link glycosylate said antibody or said antibody fragment.
83 . The method of claim 81 or 82 wherein said antibody or said antibody fragment does not possess O-linked glycosylation.
84 . The method of claim 81 or 82 wherein an active agent is conjugated to said antibody or said antibody fragment.