Chimeric, human and humanized anti-granulocyte antibodies and methods of use
AssigneeImmunomedics, Inc.
InventorsDavid Goldenberg, Hans Hansen, Shui-on Leung
Life of this patent
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Abstract
The present invention provides humanized, chimeric and human MN3 antibodies, fusion proteins, and fragments thereof. The antibodies, fusion proteins, and fragments thereof, as well as combinations with other suitable antibodies, are useful for the treatment and diagnosis of granulocyte related disorders and diseases, such as leukemia.
Claims106
A monoclonal antibody (Mab) or fragment thereof that binds NCA90 or NCA95, wherein when the Mab or fragment thereof binds NCA90 the Mab or fragment thereof is chimeric, partially humanized or fully humanized and wherein when the Mab or fragment thereof binds NCA95 the Mab or fragment thereof is either fully humanized or chimeric, partially humanized or fully humanized BW 250/183.
A CDR-grafted humanized heavy chain comprising the complementarity determining regions (CDRs) of a MN3 MAb and the framework region of the heavy chain variable region of a human antibody and the heavy chain constant region of a human antibody, wherein the CDRs of the heavy chain variable region of the humanized MN3 MAb comprise a CDR1 comprising an amino acid sequence of NYGMN (SEQ ID NO:
- 4), a CDR2 comprising an amino acid sequence of WINTYTGEPTYADDFKG (SEQ ID NO:
- 5), and a CDR3 comprising an amino acid sequence of KGWMDFNSSLDY (SEQ ID NO:
- 6).
A CDR-grafted humanized light chain comprising the complementarity determining regions (CDRs) of a MN3 MAb and the framework region of the light chain variable region of a human antibody and the light chain constant region of a human antibody, wherein the CDRs of the light chain variable region of the humanized MN3 MAb comprise a CDR1 comprising an amino acid sequence RSSQSIVHSNGNTYLE (SEQ ID NO:
- 1), a CDR2 comprising an amino acid sequence KVSNRFS (SEQ ID NO:
- 2) and a CDR3 comprising an amino acid sequence FQGSHVPPT (SEQ ID NO:
- 3).
The method of 71, wherein the subject is a human.
The method of 71, wherein the subject is a domestic pet.
The method of 71, wherein the subject is selected from the group consisting of a horse, dog, and cat.
A kit useful for treating or identifying diseased tissues in a subject comprising:
- (A) a bi-specific antibody or antibody fragment having at least one arm that specifically binds a targeted tissue and at least one other arm that specifically binds a targetable conjugate, wherein the one arm that specifically binds a targeted tissue is a granulocyte antibody or fragment thereof;
- (B) a first targetable conjugate which comprises a carrier portion which comprises or bears at least one epitope recognizable by the at least one other arm of the bi-specific antibody or antibody fragment, and one or more conjugated therapeutic or diagnostic agents;
- and
- (C) optionally, a clearing composition useful for clearing non-localized antibodies and antibody fragments;
- and
- (D) optionally, when the therapeutic agent conjugated to the first targetable conjugate is an enzyme,
- (i) a prodrug, when the enzyme is capable of converting the prodrug to a drug at the target site;
- or
- (ii) a drug which is capable of being detoxified in the subject to form an intermediate of lower toxicity, when the enzyme is capable of reconverting the detoxified intermediate to a toxic form, and, therefore, of increasing the toxicity of the drug at the target site, or
- (iii) a prodrug which is activated in the subject through natural processes and is subject to detoxification by conversion to an intermediate of lower toxicity, when the enzyme is capable of reconverting the detoxified intermediate to a toxic form, and, therefore, of increasing the toxicity of the drug at the target site, or
- (iv) a second targetable conjugate which comprises a carrier portion which comprises or bears at least one epitope recognizable by the at least one other arm of the bi-specific antibody or antibody fragment, and a prodrug, when the enzyme is capable of converting the prodrug to a drug at the target site.
Dependencies are inferred from the claim text.