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Antybody therapy

A technology of antibody and therapeutic agent, applied in the field of antibody therapy

Inactive Publication Date: 2006-12-13
IMMUNOMEDICS INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, patients treated with drugs or radionuclides conjugated with murine monoclonal antibodies (which are the most commonly targeted antibodies to humans) develop circulating human anti-mouse antibodies (HAMAs), sometimes with conjugates Generalized immediate type III hypersensitivity reaction to the antibody site

Method used

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Experimental program
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Embodiment approach

[0132] CLAIMS 1. A composition comprising at least one anti-CEA monoclonal antibody (MAb) or fragment thereof and at least one therapeutic agent. The composition of embodiment 1, wherein the anti-CEA MAb is a class I, class II or class III anti-CEA MAb, and when the MAb is a class I or class II MAb and reacts with granulocytes, the MAb is a MAb Unit price form.

[0133]2. The composition of embodiment 1, wherein the anti-CEA MAb or fragment thereof is humanized, and wherein the humanized MAb substantially retains the anti-CEA binding specificity of the murine anti-CEA MAb.

[0134] 3. The composition of embodiment 1, wherein said anti-CEA MAb or fragment thereof is a chimeric MAb, and wherein said chimeric MAb substantially retains the anti-CEA binding specificity of a murine anti-CEA MAb.

[0135] 4. The composition of embodiment 1, wherein said anti-CEA MAb or fragment thereof is an intact human MAb, and wherein said human MAb substantially retains the anti-CEA binding spec...

Embodiment 1

[0254] Example 1: Materials and methods

[0255] Monoclonal Antibodies and Cell Lines

[0256] A human thyroid myeloid cell line, TT, was purchased from the American Type Culture Center. The cell monolayer was grown in DMEM (Life Technologies, Gaithersburg, MD) supplemented with 10% fetal bovine serum, penicillin (100 U / ml), streptomycin (100 pg / ml) and L-glutamine (2mM). Cells were routinely passaged after detachment with trypsin, 0.2% EDTA.

[0257] MN-14 is a class III anti-CEA MAb reactive with CEA and unreactive with the normal cross-reactive antigens NCA and meconium antigen (Hansen et al., Cancer, 71:3478 (1993)). The construction and characterization of humanized versions of MN-14 and LL2, the anti-CD22 MAb used here as negative controls, has been presented previously. (Sharkey et al., Cancer Res., 55:5935s (1995); Leung et al., Mol. Immunol., 32:1416 (1995)). P3 x 63Ag8 (MOPC-21) is an unrelated mouse myeloma IgGl obtained from the American Type Culture Center (R...

Embodiment 2

[0260] Example 2. Combination therapy of naked hMN-14 and DTIC delivered 2 days after injection of TT (human medullary thyroid) tumor cells

[0261]In the previous study, 100 μg and 25 μg doses of DTIC (days 2, 3 and 4) and 250 μg doses of hMN-14 given weekly on day 2 and thereafter in combination with TT were used 2 days after tumor implantation. Naked hMN-14 and dacarbazine were administered. A DTIC dose of 100 [mu]g combined with hMN-14 was more effective than either treatment alone (Fig. 1A). However, a dose of 100 μg of DTIC produced too strong a response, while a dose of 25 μg was ineffective. Surprisingly, the effects of MN-14 alone and DTIC alone were not additive. In other words, given the results of treatment with 250 μg hMN-14 alone and 100 μg DTIC alone, it would not have been predicted that the combination of 250 μg hMN-14 and 100 μg DTIC would have such a significant effect. See Figure 1A.

[0262] In this study, as in previous studies, treatment started 2 da...

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Abstract

The present invention provides a composition comprising naked humanized, chimeric and human anti-CEA monoclonal antibody and a therapeutic agent, which is useful for the treatement of CEA expressing cancers and other diseases, and methods of treatment using this composition.

Description

[0001] related application [0002] This application is a continuation-in-part of US Provisional Application No. 60 / 467,161, filed May 2, 2003. This application also claims priority to International Application No. PCT / US / 02 / 32307, filed October 11, 2002, which in turn claims U.S. Provisional Application, filed October 8, 2002 Priority No. 60 / 416,531. Background of the invention [0003] A. Field of Invention [0004] The present invention relates to the treatment of cancers expressing carcinoembryonic antigen ("CEA"), particularly medullary thyroid carcinoma (MTC), non-MTC, colorectal cancer, hepatocellular carcinoma, gastric cancer, lung cancer, breast cancer and other methods of CEA-expressing cancers, wherein said treatment is by administering an immunological agent comprising an antibody in combination with at least one other therapeutic agent, such as another antibody, chemotherapy, agents, radioactive agents, antisense oligonucleot...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/00C07K16/00A61K39/395A61K51/10C07K16/30
CPCC07K16/3007A61K39/39558A61K51/1045A61K51/1096A61K2039/505A61K2039/545C07K2317/24A61P35/00A61P43/00C07K2317/73A61K2300/00A61K39/395C07K16/00
Inventor D·M·高登伯H·J·汉森
Owner IMMUNOMEDICS INC
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