Antibodies That Immunospecifically Bind to TRAIL Receptors
First Claim
1. A method of inducing apoptosis of a TR4-expressing cell, comprising contacting said cell with an isolated antibody or fragment thereof selected from the group consisting of:
- (a) an amino acid sequence that is at least 80% identical to a VH domain of any one of SEQ ID NOS;
42-53;
(b) an amino acid sequence that is at least 80% identical to a VL domain of any one of SEQ ID NOS;
42-53; and
(c) both (a) and (b);
in combination with a second agent selected from the group consisting of;
(i) an alkylating agent;
(ii) an antimetabolite;
(iii) a farnesyl transferase inhibitor;
(iv) a mitotic spindle inhibitor;
(v) a topoisomerase inhibitor;
(vi) a tyrosine kinase inhibitor;
(vii) an antibiotic;
(viii) an IAP inhibitor;
(ix) a histone deacetylase inhibitor;
(x) a HSP90 inhibitor;
(xi) thalidomide;
(xii) a thalidomide analog;
(xiii) a monoclonal antibody;
(xiv) radiation therapy;
(xv) a PPAR-gamma antagonist;
(xvi) a AKT/mTOR signaling pathway inhibitor;
(xvii) a BCL-2 inhibitor; and
(xviii) NPI-0052.wherein said antibody or fragment thereof immunospecifically binds TR4.
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Accused Products
Abstract
The present invention relates to antibodies and related molecules that immunospecifically bind to TRAIL receptor, TR4. Such antibodies have uses, for example, in the prevention and treatment of cancers and other proliferative disorders. The invention also relates to nucleic acid molecules encoding anti-TR4 antibodies, vectors and host cells containing these nucleic acids, and methods for producing the same. The present invention relates to methods and compositions for preventing, detecting, diagnosing, treating or ameliorating a disease or disorder, especially cancer and other hyperproliferative disorders, comprising administering to an animal, preferably a human, an effective amount of one or more antibodies or fragments or variants thereof, or related molecules, that immunospecifically bind to TRAIL receptor TR4.
178 Citations
65 Claims
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1. A method of inducing apoptosis of a TR4-expressing cell, comprising contacting said cell with an isolated antibody or fragment thereof selected from the group consisting of:
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(a) an amino acid sequence that is at least 80% identical to a VH domain of any one of SEQ ID NOS;
42-53;(b) an amino acid sequence that is at least 80% identical to a VL domain of any one of SEQ ID NOS;
42-53; and(c) both (a) and (b); in combination with a second agent selected from the group consisting of; (i) an alkylating agent; (ii) an antimetabolite; (iii) a farnesyl transferase inhibitor; (iv) a mitotic spindle inhibitor; (v) a topoisomerase inhibitor; (vi) a tyrosine kinase inhibitor; (vii) an antibiotic; (viii) an IAP inhibitor; (ix) a histone deacetylase inhibitor; (x) a HSP90 inhibitor; (xi) thalidomide; (xii) a thalidomide analog; (xiii) a monoclonal antibody; (xiv) radiation therapy; (xv) a PPAR-gamma antagonist; (xvi) a AKT/mTOR signaling pathway inhibitor; (xvii) a BCL-2 inhibitor; and (xviii) NPI-0052. wherein said antibody or fragment thereof immunospecifically binds TR4. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29)
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30. A method of treating a TR4-expressing cancer, comprising administering to an animal an isolated antibody or fragment thereof selected from the group consisting of:
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(a) an amino acid sequence that is at least 80% identical to a VH domain of any one of SEQ ID NOS;
42-53;(b) an amino acid sequence that is at least 80% identical to a VL domain of any one of SEQ ID NOS;
42-53; and(c) both (a) and (b); in combination with a second agent selected from the group consisting of; (i) an alkylating agent; (ii) an antimetabolite; (iii) a farnesyl transferase inhibitor; (iv) a mitotic spindle inhibitor; (v) a topoisomerase inhibitor; (vi) a tyrosine kinase inhibitor; (vii) an antibiotic; (viii) an IAP inhibitor; (ix) a histone deacetylase inhibitor; (x) a HSP90 inhibitor; (xi) thalidomide; (xii) a thalidomide analog; (xiii) a monoclonal antibody; (xiv) radiation therapy; (xv) a PPAR-gamma antagonist; (xvi) a AKT/mTOR signaling pathway inhibitor; (xvii) a BCL-2 inhibitor; and (xviii) NPI-0052. wherein said antibody or fragment thereof immunospecifically binds TR4. - View Dependent Claims (31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58)
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59. A method of treating a TR4-expressing cancer, comprising administering to an animal an isolated antibody or fragment thereof selected from the group consisting of:
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(a) an amino acid sequence that is at least 80% identical to a VH domain of any one of SEQ ID NOS;
42-53;(b) an amino acid sequence that is at least 80% identical to a VL domain of any one of SEQ ID NOS;
42-53; and(c) both (a) and (b); wherein said cancer is selected from the group consisting of; (i) multiple myeloma; (ii) bile duct carcinoma; (iii) hepatoma; and (iv) lung cancer; wherein said antibody or fragment thereof immunospecifically binds TR4. - View Dependent Claims (60, 61, 62, 63)
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64. A method of treating hepatitis C, comprising administering to a patient an isolated antibody or fragment thereof selected from the group consisting of:
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(a) an amino acid sequence that is at least 80% identical to a VH domain of any one of SEQ ID NOS;
42-53;(b) an amino acid sequence that is at least 80% identical to a VL domain of any one of SEQ ID NOS;
42-53; and(c) both (a) and (b); wherein said antibody or fragment thereof immunospecifically binds TR4.
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65. An isolated antibody or fragment thereof comprising the VHCDR3 region of any one of SEQ ID NOS:
- 42-53, wherein said antibody or fragment thereof immunospecifically binds TR4.
Specification