# US 2013/0156691 A1 · Antibody Therapy

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- Number: US 2013/0156691 A1
- Document ID: US20130156691A1
- Status: Published application
- Kind: A1
- Application number: 13/476,157
- Filed: 2012-05-21
- Published: 2013-06-20
- Earliest claimed: 2002-10-11
- Assignees: Immunomedics, Inc.
- Inventors: David M. Goldenberg; Hans J. Hansen
- Web page: https://patentgrep.com/patent/US20130156691A1

## CPC

- A61K 39/39558: {against tumor tissues, cells, antigens}
- A61K 31/437: the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
- A61K 31/4545: containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
- 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)
- A61K 31/475: having an indole ring, e.g. yohimbine, reserpine, strychnine, vinblastine (vincamine A61K31/4375)
- A61K 31/513: having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
- A61K 31/519: ortho- or peri-condensed with heterocyclic rings
- A61K 31/555: containing heavy metals, e.g. hemin, hematin, melarsoprol
- A61K 31/655: Azo (—N=N—), diazo (=N2), azoxy (>N—O—N< or N(=O)—N<), azido (—N3) or diazoamino (—N=N—N<) compounds
- A61K 31/675: having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
- A61K 31/704: attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin {(digitoxin A61K31/7048)}
- A61K 38/164: {from bacteria}
- A61K 38/168: {from plants}
- A61K 38/1816: {Erythropoietin [EPO]}
- A61K 38/191: {Tumor necrosis factors [TNF], e.g. lymphotoxin [LT], i.e. TNF-beta}
- A61K 38/193: {Colony stimulating factors [CSF]}
- A61K 38/196: {Thrombopoietin}
- A61K 38/20: Interleukins [IL]
- A61K 38/217: {IFN-gamma}
- A61K 51/1045: {against animal or human tumor cells or tumor cell determinants}
- A61K 51/1048: {the tumor cell determinant being a carcino embryonic antigen}
- A61K 51/1096: {radioimmunotoxins, i.e. conjugates being structurally as defined in A61K51/1093, and including a radioactive nucleus for use in radiotherapeutic applications}
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 35/00: Antineoplastic agents
- A61P 37/04: Immunostimulants
- C07K 16/3007: {Carcino-embryonic Antigens}
- A61K 2039/505: {comprising antibodies}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)

## 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

### Claim 1

A method for treating a CEA expressing cancer comprising:
a) administering to a subject with a CEA expressing cancer a naked Class I monovalent anti-CEA monoclonal antibody (MAb) or antigen-binding fragment thereof;
b) administering to the subject either concurrently or sequentially a naked Class III anti-CEA antibody or antigen-binding fragment thereof, wherein (i) the naked Class III anti-CEA antibody or fragment thereof is unreactive with human granulocytes; (ii) the naked Class III anti-CEA antibody or fragment thereof has human IgG1 hinge and constant regions; (iii) administration of the naked Class III anti-CEA antibody or fragment thereof to a subject with a cancer that expresses CEA antigen sensitizes the cancer to the subsequent administration of a therapeutic agent; and
c) administering to the subject either concurrently or sequentially at least one therapeutic agent.

### Claim 2 (depends on 1)

The method of claim 1, wherein the therapeutic agent is selected from the group consisting of an antibody, an antigen-binding antibody fragment, an immunoconjugate, a cytotoxic agent, a chemotherapeutic agent, a radionuclide, an immunomodulator, a photoactive therapeutic agent, an antisense oligonucleotide and a hormone.

### Claim 3 (depends on 2)

The method of claim 2, wherein the therapeutic agent comprises vincristine, doxorubicin, DTIC, cyclophosphamide, CPT-11, oxaliplatin, gemcitabine and 5-fluorouracil/leucovorin.

### Claim 4 (depends on 2)

The method of claim 2, wherein the therapeutic agent is selected from the group consisting of vincristine, doxorubicin, DTIC, cyclophosphamide, CPT-11, oxaliplatin, gemcitabine and 5-fluorouracil/leucovorin.

### Claim 5 (depends on 2)

The method of claim 2, wherein the therapeutic agent is a naked antibody or an immunoconjugate.

### Claim 6 (depends on 5)

The method of claim 5, wherein said naked antibody or immunoconjugate comprises a humanized, chimeric, human or murine antibody or fragment thereof reactive with an antigen selected from the group consisting of EGP-1, EGP-2, MUC-1, MUC-2, MUC-3, MUC-4, antigen bound by PAM4 antibody, KC4, TAG-72, EGFR, HER2/neu, BrE3, Le-Y, A3, A33, Ep-CAM, Tn, Thomson-Friedenreich antigens, tumor necrosis antigens, VEGF, a tumor angiogenesis antigen, Ga 733, tenascin and fibronectin.

### Claim 7 (depends on 1)

The method of claim 1, wherein the cancer is medullary thyroid carcinoma or colon cancer.

### Claim 8 (depends on 2)

The method of claim 2, wherein the cytotoxic agent is a drug or toxin.

### Claim 9 (depends on 8)

The method of claim 8, wherein the drug possesses a pharmaceutical property selected from the group consisting of antimitotic, alkylating, antimetabolite, antiangiogenic, apoptotic, alkaloid, COX-2, and antibiotic agents and combinations thereof.

### Claim 10 (depends on 8)

The method of claim 8, wherein the drug 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, enzymes, epipodophyllotoxins, platinum coordination complexes, vinca alkaloids, substituted ureas, methyl hydrazine derivatives, adrenocortical suppressants, antagonists, endostatin, taxols, camptothecins, doxorubicins and a combination thereof.

### Claim 11 (depends on 8)

The method of claim 8, wherein the toxin is a microbial, plant or animal toxin 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.

### Claim 12 (depends on 2)

The method of claim 2, wherein the 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.

### Claim 13 (depends on 2)

The method of claim 2, wherein the immunomodulator comprises IL-1, IL-2, IL-3, IL-6, IL-10, IL-12, IL-18, interferon-γ, TNF-α or a combination thereof.

### Claim 14 (depends on 2)

The method of claim 2, wherein the 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.

### Claim 15 (depends on 1)

The method of claim 1, wherein the subject has a colon, rectal, pancreatic, breast, ovarian, thyroid or lung cancer.

### Claim 16 (depends on 1)

The method of claim 1, wherein said antibody fragment is selected from the group consisting of a F(ab′)2, a Fab′, a Fab, an Fv and an scFv.

### Claim 17 (depends on 1)

The method of claim 1, wherein the Class I anti-CEA antibody is MN-3 or MN-15.

### Claim 18 (depends on 1)

The method of claim 1, wherein the Class III anti-CEA antibody is MN-14.

### Claim 19 (depends on 1)

The method of claim 1, wherein the Class III anti-CEA antibody is a G1m3 allotype antibody.

### Claim 20 (depends on 1)

The method of claim 1, wherein the Class III anti-CEA antibody is an nG1m1 allotype antibody.