Antibody therapy

• US 7,662,378 B2
• Filed: 10/31/2007
• Issued: 02/16/2010
• Est. Priority Date: 10/08/2002
• Status: Active Grant

• Current Assignee: Immunomedics, Inc.
• Original Assignee: Immunomedics, Inc.
• Inventors: Goldenberg, David M., Hansen, Hans J.
• Primary Examiner(s): Yaen; Christopher H
• Application Number:
  US11/932,530
• Publication Number:
  US 20090092598A1
• Time in Patent Office: 839 Days
• Field of Search: 424/130.1
• US Class Current: 424/130.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/437 the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• CPC Class Codes: A61K 31/4545 containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
• CPC Class Codes: A61K 31/4745 condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48
• CPC Class Codes: A61K 31/475 having an indole ring, e.g. yohimbine, reserpine, strychnine, vinblastine vincamine A61K31/4375
• CPC Class Codes: A61K 31/513 having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 31/555 containing heavy metals, e.g. hemin, hematin, melarsoprol
• CPC Class Codes: A61K 31/655 Azo (—N=N—), diazo (=N2), azoxy (>N—O—N< or N(=O)—N<), azido (—N3) or diazoamino (—N=N—N<) compounds
• CPC Class Codes: A61K 31/675 having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
• CPC Class Codes: A61K 31/704 attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin digitoxin A61K31/7048
• CPC Class Codes: A61K 38/164 from bacteria
• CPC Class Codes: A61K 38/168 from plants
• CPC Class Codes: A61K 38/1816 Erythropoietin [EPO]
• CPC Class Codes: A61K 38/191 Tumor necrosis factors [TNF], e.g. lymphotoxin [LT], i.e. TNF-beta
• CPC Class Codes: A61K 38/193 Colony stimulating factors [CSF]
• CPC Class Codes: A61K 38/196 Thrombopoietin
• CPC Class Codes: A61K 38/20 Interleukins [IL]
• CPC Class Codes: A61K 38/217 IFN-gamma
• CPC Class Codes: A61K 39/39558 : against tumor tissues, cells, antigens
• CPC Class Codes: A61K 51/1045 : against animal or human tumor cells or tumor cell determinants
• CPC Class Codes: A61K 51/1048 : the tumor cell determinant being a carcino embryonic antigen
• CPC Class Codes: A61K 51/1096 : radioimmunotoxins, i.e. conjugates being structurally as defined in A61K51/1093, and including a radioactive nucleus for use in radiotherapeutic applications
• CPC Class Codes: A61P 31/00 : Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 37/04 : Immunostimulants
• CPC Class Codes: C07K 16/3007 : Carcino-embryonic Antigens
• CPC Class Codes: C07K 2317/24 : containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered

Abstract

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

Claims

1. A method for treating a CEA and/or NCA expressing carcinoma comprising:

a) administering to a subject with a CEA and/or NCA expressing carcinoma a monovalent Class I anti-CEA monoclonal antibody (MAb) or antigen-binding fragment thereof, wherein the MAb or fragment thereof is a monovalent chimeric or humanized MN-3 or MN-15 antibody; and

b) administering either concurrently or sequentially at least one anti-cancer therapeutic agent.

2. The method of claim 1, wherein said therapeutic agent is selected from the group consisting of a naked antibody, a cytotoxic agent, a drug, a toxin, a radionuclide, an immunomodulator, a photoactive therapeutic agent, a radiosensitizing agent and a hormone.

3. The method of claim 1, wherein the CEA, and/or NCA expressing carcinoma is a colon, rectal, pancreatic, breast, ovarian, thyroid, or lung carcinoma.

5. The method of claim 1, wherein said therapeutic agent is selected from the group consisting of vincristine, doxorubicin, dacarbazine (DTIC), cyclophosphamide, CPT-11, oxaliplatin, gemcitabine and 5-fluorouracil/leucovorin.

6. The method of claim 1, wherein said therapeutic agent is a naked antibody or an antigen-binding fragment thereof.

7. The method of claim 2, wherein said cytotoxic agent is selected from the group consisting of nitrogen mustards, ethylenimine derivatives, alkyl sulfonates, nitrosoureas, triazenes, folic acid analogs, anthracyclines, taxanes, COX-2 inhibitors, pyrimidine analogs, purine analogs, antimetabolites, antibiotics, epipodophyllotoxins, platinum coordination complexes, vinca alkaloids, substituted ureas, methyl hydrazine derivatives, adrenocortical suppressants, endostatin, taxols, camptothecins, oxaliplatin, doxorubicin and doxorubicin analogs.

8. The method of claim 2, wherein said toxin is selected from the group consisting of ricin, abrin, alpha toxin, saporin, ribonuclease (RNase), DNase I, Staphylococcal enterotoxin-A, pokeweed antiviral protein, gelonin, diphtheria toxin, Pseudomonas exotoxin, and Pseudomonas endotoxin.

9. The method of claim 2, wherein said immunomodulator is selected from the group consisting of a cytokine, a stem cell growth factor, a lymphotoxin, a hematopoietic factor, a colony stimulating factor (CSF), an interferon (IFN), erythropoietin, thrombopoietin, tumor necrosis factor (TNF), an interleukin (IL), granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), interferon-alpha., interferon-beta, interferon-gamma, a stem cell growth factor designated “

S1 factor,”

IL-1, IL-2, IL-3, IL-6, IL-10, IL-12, IL-18 and IL-21.

10. The method of claim 2, wherein said radionuclide is selected from the group consisting of ³²P, ³³P, ⁴⁷Sc, ⁵⁹Fe, ⁶⁴Cu, ⁶⁷Cu, ⁷⁵Se, ⁷⁷As, ⁸⁹Sr, ⁹⁰Y, ⁹⁹Mo, ¹⁰⁵Rh, ¹⁰⁹Pd, ¹¹¹Ag, ¹²⁵I, ¹³¹I, ¹⁴²Pr, ¹⁴³Pr, ¹⁴⁹Pm, ¹⁵³Sm, ¹⁶¹Tb, ¹⁶⁶Ho, ¹⁶⁹Er, ¹⁷⁷Lu, ¹⁸⁶Re, ¹⁸⁸Re, ¹⁸⁹Re, ¹⁹⁴Ir, ¹⁹⁸Au, ¹⁹⁹Au, ²¹¹Pb, ²¹²Pb, ²¹³Bi, ⁵⁸Co, ⁶⁷Ga, ^80mBr, ^99mTc, ^103mRh, ¹⁰⁹Pt, ¹¹¹In, ¹¹⁹Sb, ¹⁶¹Ho, ^189mOs, ¹⁹²Ir, ¹⁵²Dy, ²¹¹At, ²¹²Bi, ²²³Ra, ²¹⁹Rn, ²¹⁵Po, ²¹¹Bi, ²²⁵Ac, ²²¹Fr, ²¹⁷At, ²¹³Bi, ⁸⁸Y, and ²²⁵Fm.

4. A method for treating a CEA and/or NCA expressing carcinoma comprising:

a) administering to a subject with a CEA and/or NCA expressing carcinoma a monovalent Class I anti-CEA monoclonal antibody (MAb) or antigen-binding fragment thereof, wherein said antibody fragment is selected from the group consisting of a Fab′

, a Fab, an Fv and an scFv; and

b) administering either concurrently or sequentially at least one anti-cancer therapeutic agent.

11. The method of claim 4, wherein said therapeutic agent is selected from the group consisting of a naked antibody, a cytotoxic agent, a drug, a toxin, a radionuclide, an immunomodulator, a photoactive therapeutic agent, a radiosensitizing agent and a hormone.

12. The method of claim 4, wherein the CEA, and/or NCA expressing carcinoma is a colon, rectal, pancreatic, breast, ovarian, thyroid, or lung carcinoma.

13. The method of claim 4, wherein said therapeutic agent is selected from the group consisting of vincristine, doxorubicin, dacarbazine (DTIC), cyclophosphamide, CPT-11, oxaliplatin, gemcitabine and 5-fluorouracil/leucovorin.

14. The method of claim 4, wherein said therapeutic agent is a naked antibody or an antigen-binding fragment thereof.

15. The method of claim 11, wherein said cytotoxic agent is selected from the group consisting of nitrogen mustards, ethylenimine derivatives, alkyl sulfonates, nitrosoureas, triazenes, folic acid analogs, anthracyclines, taxanes, COX-2 inhibitors, pyrimidine analogs, purine analogs, antimetabolites, antibiotics, epipodophyllotoxins, platinum coordination complexes, vinca alkaloids, substituted ureas, methyl hydrazine derivatives, adrenocortical suppressants, endostatin, taxols, camptothecins, oxaliplatin, doxorubicin and doxorubicin analogs.

16. The method of claim 11, wherein said toxin is selected from the group consisting of ricin, abrin, alpha toxin, saporin, ribonuclease (RNase), DNase I, Staphylococcal enterotoxin-A, pokeweed antiviral protein, gelonin, diphtheria toxin, Pseudomonas exotoxin, and Pseudomonas endotoxin.

17. The method of claim 11, wherein said immunomodulator is selected from the group consisting of a cytokine, a stem cell growth factor, a lymphotoxin, a hematopoietic factor, a colony stimulating factor (CSF), an interferon (IFN), erythropoietin, thrombopoietin, tumor necrosis factor (TNF), an interleukin (IL), granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), interferon-alpha., interferon-beta, interferon-gamma, a stem cell growth factor designated “

S1 factor,”

IL-1, IL -2, IL-3, IL-6, IL-10, IL-12, IL-18 and IL-21.

18. The method of claim 11, wherein said radionuclide is selected from the group consisting of ³²P, ³³P, ⁴⁷Sc, ⁵⁹Fe, ⁶⁴Cu, ⁶⁷Cu, ⁷⁵Se, ⁷⁷As, ⁸⁹Sr, ⁹⁰Y, ⁹⁹Mo, ¹⁰⁵Rh, ¹⁰⁹Pd, ¹¹¹Ag, ¹²⁵I, ¹³¹I, ¹⁴²Pr, ¹⁴³Pr, ¹⁴⁹Pm, ¹⁵³Sm, ¹⁶¹Tb, ¹⁶⁶Ho, ¹⁶⁹Er, ¹⁷⁷Lu, ¹⁸⁶Re, ¹⁸⁸Re, ¹⁸⁹Re, ¹⁹⁴Ir, ¹⁹⁸Au, ¹⁹⁹Au, ²¹¹Pb, ²¹²Pb, ²¹³Bi, ⁵⁸Co, ⁶⁷Ga, ^80mBr, ^99mTc, ^103mRh, ¹⁰⁹Pt, ¹¹¹In, ¹¹⁹Sb, ¹⁶¹Ho, ^189mOs, ¹⁹²Ir, ¹⁵²Dy, ²¹¹At, ²¹²Bi, ²²³Ra, ²¹⁹Rn, ²¹⁵Po, ²¹¹Bi, ²²⁵Ac, ²²¹Fr, ²¹⁷At, ²¹³Bi, ⁸⁸Y and ²⁵⁵Fm.