Methods for treating cancer using anti-PD-1 antibodies in combination with anti-CTLA-4 antibodies
First Claim
1. A method of inhibiting tumor growth in a subject having a tumor that does not express PD-L1 comprising administering to the subject a combination of a dose of an anti-PD-1 monoclonal antibody or an antigen-binding portion thereof and a dose of an anti-CTLA-4 monoclonal antibody or an antigen-binding portion thereof, wherein the combination of the anti-PD-1 antibody or antigen-binding portion thereof and the anti-CTLA-4 antibody or antigen-binding portion thereof inhibits growth of the tumor in the subject.
6 Assignments
0 Petitions
Accused Products
Abstract
The present invention provides isolated monoclonal antibodies, particularly human monoclonal antibodies, that specifically bind to PD-1 with high affinity. Nucleic acid molecules encoding the antibodies of the invention, expression vectors, host cells and methods for expressing the antibodies of the invention are also provided. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of the invention are also provided. The invention also provides methods for detecting PD-1, as well as methods for treating various diseases, including cancer and infectious diseases, using anti-PD-1 antibodies. The present invention further provides methods for using a combination immunotherapy, such as the combination of anti-CTLA-4 and anti-PD-1 antibodies, to treat hyperproliferative disease, such as cancer. The invention also provides methods for altering adverse events related to treatment with such antibodies individually.
139 Citations
49 Claims
- 1. A method of inhibiting tumor growth in a subject having a tumor that does not express PD-L1 comprising administering to the subject a combination of a dose of an anti-PD-1 monoclonal antibody or an antigen-binding portion thereof and a dose of an anti-CTLA-4 monoclonal antibody or an antigen-binding portion thereof, wherein the combination of the anti-PD-1 antibody or antigen-binding portion thereof and the anti-CTLA-4 antibody or antigen-binding portion thereof inhibits growth of the tumor in the subject.
- 3. A method of reducing the size of a tumor that does not express PD-L1 in a subject having said tumor comprising administering to the subject a combination of a dose of an anti-PD-1 monoclonal antibody or an antigen-binding portion thereof and a dose of an anti-CTLA-4 monoclonal antibody or an antigen-binding portion thereof, wherein the combination of the anti-PD-1 antibody or antigen-binding portion thereof and the anti-CTLA-4 antibody or antigen-binding portion thereof reduces the size of the tumor in the subject.
- 5. A method of treating cancer in a subject having a tumor that does not express PD-L1 comprising administering to the subject a combination of a dose of an anti-PD-1 monoclonal antibody or an antigen-binding portion thereof and a dose of an anti-CTLA-4 monoclonal antibody or an antigen-binding portion thereof, wherein the combination of the anti-PD-1 antibody or antigen-binding portion thereof and the anti-CTLA-4 antibody or antigen-binding portion thereof treats cancer in the subject.
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9. A method of inhibiting tumor growth in a subject in need thereof comprising administering to the subject a combination of a dose of an anti-PD-1 monoclonal antibody or an antigen-binding portion thereof and a dose of an anti-CTLA-4 monoclonal antibody or an antigen-binding portion thereof;
- wherein the dose of the anti-PD-1 antibody or antigen-binding portion thereof, the dose of the anti-CTLA-4 antibody or antigen-binding portion thereof, or both doses are subtherapeutic doses; and
wherein the combination of the anti-PD-1 antibody or antigen-binding portion thereof and the anti-CTLA-4 antibody or antigen-binding portion thereof inhibits tumor growth in the subject. - View Dependent Claims (10, 11, 12)
- wherein the dose of the anti-PD-1 antibody or antigen-binding portion thereof, the dose of the anti-CTLA-4 antibody or antigen-binding portion thereof, or both doses are subtherapeutic doses; and
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13. A method of reducing the size of a tumor in a subject in need thereof comprising administering to the subject a combination of a dose of an anti-PD-1 monoclonal antibody or an antigen-binding portion thereof and a dose of an anti-CTLA-4 monoclonal antibody or an antigen-binding portion thereof;
- wherein the dose of the anti-PD-1 antibody or antigen-binding portion thereof, the dose of the anti-CTLA-4 antibody or antigen-binding portion thereof, or both doses are subtherapeutic doses; and
wherein the combination of the anti-PD-1 antibody or antigen-binding portion thereof and the anti-CTLA-4 antibody or antigen-binding portion thereof reduces the tumor size in the subject. - View Dependent Claims (14, 15, 16)
- wherein the dose of the anti-PD-1 antibody or antigen-binding portion thereof, the dose of the anti-CTLA-4 antibody or antigen-binding portion thereof, or both doses are subtherapeutic doses; and
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17. A method of treating cancer comprising administering to a subject in need thereof a combination of a dose of an anti-PD-1 monoclonal antibody or an antigen-binding portion thereof and a dose of an anti-CTLA-4 monoclonal antibody or an antigen-binding portion thereof;
- wherein the dose of the anti-PD-1 antibody or antigen-binding portion thereof, the dose of the anti-CTLA-4 antibody or antigen-binding portion thereof, or both doses are subtherapeutic doses; and
wherein the combination of the anti-PD-1 antibody or antigen-binding portion thereof and the anti-CTLA-4 antibody or antigen-binding portion thereof treats cancer in the subject. - View Dependent Claims (18, 19, 20, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49)
- wherein the dose of the anti-PD-1 antibody or antigen-binding portion thereof, the dose of the anti-CTLA-4 antibody or antigen-binding portion thereof, or both doses are subtherapeutic doses; and
- 21. A method of conferring persistent immunity to tumor relapse in a subject in need thereof comprising administering to the subject a combination of a dose of an anti-PD-1 monoclonal antibody or an antigen-binding portion thereof and a dose of an anti-CTLA-4 monoclonal antibody or an antigen-binding portion thereof, wherein the combination of the anti-PD-1 antibody or antigen-binding portion thereof and the anti-CTLA-4 antibody or antigen-binding portion thereof confers persistent immunity to tumor relapse.
- 24. A method of reducing the incidence of an adverse event induced by a therapeutic dose of an anti-CTLA-4 monoclonal antibody or an antigen-binding portion thereof in treating a hyperproliferative disease, in a subject in need thereof comprising administering (i) a dose of an anti-PD-1 monoclonal antibody or an antigen-binding portion thereof and (ii) a subtherapeutic dose of the anti-CTLA-4 monoclonal antibody or an antigen-binding portion thereof to the subject, wherein the subject exhibits a reduction in the adverse event after the administration.
Specification