METHODS AND COMPOSITIONS FOR TREATING CANCER AND INFECTIOUS DISEASES
First Claim
1. A method of treating, reducing the severity of and/or slowing the progression of an infectious disease or cancer in a subject in need thereof, comprising:
- providing a CD4 lymphocyte depleting agent;
providing at least one additional agent selected from the group consisting of an immune check point inhibitor, an adoptive immune therapeutic, an immune adjuvant, and an immune modulating agent; and
administering a therapeutically effective amount of the CD4 lymphocyte depleting agent and the additional agent to the subject, thereby treating, preventing, reducing the severity of and/or slowing the progression of the condition in the subject.
1 Assignment
0 Petitions
Accused Products
Abstract
The invention relates to compositions comprising a CD4 lymphocyte depleting agent; and methods of using the compositions to treat, prevent, reduce the severity of and/or slow the progression of a condition in a subject. The invention also relates to use of combinations of a CD4 lymphocyte depleting agent and at least one additional agent to treat, prevent, reduce the severity of and/or slow the progression of a condition in a subject. The additional agent may be an immune check point inhibitor, an adoptive immune therapeutic, an immune adjuvant, or an immune modulating agent, or their combinations.
14 Citations
29 Claims
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1. A method of treating, reducing the severity of and/or slowing the progression of an infectious disease or cancer in a subject in need thereof, comprising:
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providing a CD4 lymphocyte depleting agent; providing at least one additional agent selected from the group consisting of an immune check point inhibitor, an adoptive immune therapeutic, an immune adjuvant, and an immune modulating agent; and administering a therapeutically effective amount of the CD4 lymphocyte depleting agent and the additional agent to the subject, thereby treating, preventing, reducing the severity of and/or slowing the progression of the condition in the subject.
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2. A method of treating, reducing the severity of and/or slowing the progression of an infectious disease or cancer in a subject, comprising:
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providing a composition comprising a CD4 lymphocyte depleting agent; and administering a therapeutically effective amount of the composition to the subject, thereby treating, preventing, reducing the severity of and/or slowing the progression of the condition in the subject.
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3. (canceled)
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4. The method of claim 1, wherein the cancer is kidney cancer, melanoma, prostate cancer, breast cancer, glioblastoma, lung cancer, colon cancer, or bladder cancer.
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5. The method of claim 1, wherein the subject is a human.
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6. The method of claim 2, wherein the subject had been diagnosed with cancer or an infectious disease.
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7. (canceled)
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8. The method of claim 1, wherein the CD4 lymphocyte depleting agent is a monoclonal antibody or a fragment thereof, a polyclonal antibody or a fragment thereof, a chimeric antibody, a humanized antibody, a human antibody or a fragment thereof, or a single chain antibody.
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9. The method of claim 1, wherein the CD4 lymphocyte depleting agent is a humanized anti-CD4 antibody.
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10. The method of claim 1, wherein the CD4 lymphocyte depleting agent is zanolimumab.
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11. The method of claim 1, wherein the CD4 lymphocyte depleting agent is administered at 100-200 mg/day, 200-300 mg/day, 300-400 mg/day, 400-500 mg/day, 500-600 mg/day, 600-700 mg/day, 700-800 mg/day, 800-900 mg/day, 900-1000 mg/day, 1000-1100 mg/day, 1100-1200 mg/day, 1200-1300 mg/day, 1300-1400 mg/day, 1400-1500 mg/day, 1500-1600 mg/day, 1600-1700 mg/day, 1700-1800 mg/day, 1800-1900 mg/day or 1900-2000 mg/day.
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12. The method of claim 1, wherein the adoptive immune therapeutic agent is a dendritic cell vaccine.
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13. The method of claim 1, wherein the immune checkpoint inhibitor is an anti-PD1 antibody.
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14. The method of claim 1, wherein the composition further comprises an mTOR inhibitor.
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15. The method of claim 1, wherein the composition is administered intravenously, intramuscularly, subcutaneously, intraperitoneally, orally or via inhalation.
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16. The method of claim 1, wherein the CD4 lymphocyte depleting agent and the additional agent are administered concurrently.
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17. The method of claim 1, wherein the CD4 lymphocyte depleting agent is administered before, during or after administering the additional agent.
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18. The method of claim 1, wherein the additional agent is administered at 0.1-0.5 mg/day, 0.5-1.0 mg/day, 1.0-1.5 mg/day, 1.5-2.0 mg/day, 2.0-2.5 mg/day, 2.5-5 mg/day, 5-10 mg/day, 10-15 mg/day, 15-20 mg/day, 20-25 mg/day, 25-30 mg/day, 30-35 mg/day, 35-40 mg/day, 40-45 mg/day, 45-50 mg/day, 50-55 mg/day, 55-60 mg/day, 60-65 mg/day, 65-70 mg/day, 70-75 mg/day, 75-80 mg/day, 80-85 mg/day, 85-90 mg/day, 90-95 mg/day or 95-100 mg/day.
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19. The method of claim 1, wherein the additional agent is an immune checkpoint inhibitor.
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20. The method of claim 19, wherein the immune checkpoint inhibitor is selected from the group consisting of an antibody against PD-1, an antibody against PD-L1, an antibody against PD-L2, an antibody against CTLA-4, an antibody against KIR, an antibody against IDOL an antibody against IDO2, an antibody against TIM-3, an antibody against LAG-3, an antibody against OX40R, and an antibody against PS, or a combination thereof.
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21. The method of claim 1, wherein the additional agent is an adoptive immune therapeutic.
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22. The method of claim 21, wherein the adoptive immune therapeutic is selected from the group consisting of a dendritic cell vaccine, a peptide vaccine, a chimeric T cell antigen-based therapy, an immune cytokine, a heat shock protein-based vaccine, a tumor lysate-based vaccine, a viral vector carrying a tumor antigen, a viral vaccine, a bacterial vaccine, and a fungal vaccine, or a combination thereof.
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23. The method of claim 1, wherein the additional agent is an immune adjuvant.
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24. The method of claim 23, wherein the immune adjuvant is selected from the group consisting of an aluminum salt, a virosome and an oil-based adjuvant, or a combination thereof.
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25. The method of claim 1, wherein the additional agent is an immune modulating agent.
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26. The method of claim 25, wherein the immune modulating agent is selected from the group consisting of an mTOR inhibitor, a STAT inhibitor, a TGFβ
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27. The method of claim 14, wherein the mTOR inhibitor is selected from the group consisting of a small molecule, a peptide, an antibody or a fragment thereof, a nucleic acid molecule and a macrolide compound.
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28. The method of claim 27, wherein the mTOR inhibitor is selected from the group consisting of (i) temsirolimus (CCI-779) or a pharmaceutical equivalent, analog, derivative or a salt thereof, (ii) evirolimus (RAD-001) or a pharmaceutical equivalent, analog, derivative or a salt thereof, and (iii) sirolimus (rapamycin) or a pharmaceutical equivalent, analog, derivative or a salt thereof.
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29-33. -33. (canceled)
Specification