Claims for Patent: 9,181,340

Summary for Patent: 9,181,340

Title:	TEM8 antibodies, conjugates thereof, and their use
Abstract:	Antibodies that specifically bind TEM8 protein, and conjugates thereof, are disclosed herein. In some examples the conjugates and antibodies are useful for methods of detecting and treating pathogenic angiogenesis. In other examples the conjugates and antibodies are useful for methods of detecting and treating cancer. In additional examples, the conjugates and antibodies are useful for methods of decreasing binding of Anthrax protective antigen to a cell.
Inventor(s):	St. Croix; Brad (Frederick, MD), Fleming; Tony (Stow, MA), Chaudhary; Amit (Frederick, MD), Saha; Saurabh (Leawood, KS), Zhang; Xiaoyan Michelle (Lexington, MA), Kwong; Rou-fun (Cambridge, MA), Hilton; Mary Beth (Thurmont, MD)
Assignee:	The United States of America, as represented by the Secretary, Department of Health and Human Services (Washington, DC) Novartis AG (Basel, CH)
Application Number:	14/126,372
Patent Claims:	1. An isolated monoclonal antibody or antigen binding fragment thereof, comprising a heavy chain variable region comprising a heavy chain complementarity determining region (HCDR)1, a HCDR2, and a HCDR3, and a light chain variable region comprising a light chain complementarity determining region (LCDR)1, a LCDR2, and a L-CDR3, of the amino acid sequences set forth as one of: (a) SEQ ID NO: 1 and SEQ ID NO: 6, respectively (L2); (b) SEQ ID NO: 2 and SEQ ID NO: 7, respectively (L1); (c) SEQ ID NO: 3 and SEQ ID NO: 8, respectively (L3); (d) SEQ ID NO: 4 and SEQ ID NO: 9, respectively (L5); or (e) SEQ ID NO: 5 and SEQ ID NO: 10, respectively (1D2); and wherein the monoclonal antibody or antigen binding fragment specifically binds to TEM8. 2. The antibody or antigen binding fragment of claim 1, wherein: (a) the heavy chain variable region comprises the amino acid sequence set forth as amino acids 31-37, 52-67, and 100-106 of SEQ ID NO: 1, and the light chain variable region comprises the amino acid sequence set forth as amino acids 23-33, 49-55, and 88-96 of SEQ ID NO: 6; (b) the heavy chain variable region comprises the amino acid sequence set forth as amino acids 31-35, 50-65, and 96-102 of SEQ ID NO: 2, and the light chain variable region comprises the amino acid sequence set forth as amino acids 23-33, 49-55, and 88-98 of SEQ ID NO: 7; (c) the heavy chain variable region comprises the amino acid sequence set forth as amino acids 31-37, 52-69, and 102-110 of SEQ ID NO: 3, and the light chain variable region comprises the amino acid sequence set forth as amino acids 23-33, 49-55, and 88-96 of SEQ ID NO: 8; (d) the heavy chain variable region comprises the amino acid sequence set forth as amino acids 31-35, 50-66, and 99-106 of SEQ ID NO: 4, and the light chain variable region comprises the amino acid sequence set forth as amino acids 23-33, 49-55, and 88-98 of SEQ ID NO: 9; or (e) the heavy chain variable region comprises the amino acid sequence set forth as amino acids 31-37, 52-67, and 100-107 of SEQ ID NO: 5, and the light chain variable region comprises the amino acid sequence set forth as amino acids 23-33, 49-55, and 88-98 of SEQ ID NO: 10. 3. The antibody or antigen binding fragment of claim 1, wherein the heavy chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5; or the light chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, or SEQ ID NO: 10. 4. The antibody or antigen binding fragment of claim 1, wherein the heavy and light chain variable regions comprise the amino acid sequences set forth as one of: (a) SEQ ID NO: 1 and SEQ ID NO: 6, respectively; (b) SEQ ID NO: 2 and SEQ ID NO: 7, respectively; (c) SEQ ID NO: 3 and SEQ ID NO: 8, respectively; (d) SEQ ID NO: 4 and SEQ ID NO: 9, respectively; or (e) SEQ ID NO: 5 and SEQ ID NO: 10, respectively. 5. The antibody or antigen binding fragment of claim 1, comprising a human framework region. 6. The antibody of claim 1, wherein the antibody is an IgG. 7. The antibody or antigen binding fragment of claim 1, wherein the antibody or antigen binding fragment is neutralizing. 8. The antigen binding fragment of claim 1. 9. The antigen binding fragment of claim 8, wherein the antigen binding fragment is a Fv, Fab, F(ab').sub.2, scFV or a scFV.sub.2 fragment. 10. The antibody or antigen binding fragment of claim 1, conjugated to an effector molecule or a detectable marker. 11. The antibody or antigen binding fragment of claim 10, wherein the effector molecule is an anti-angiogenic agent or a chemotherapeutic agent. 12. The antibody or antigen binding fragment of claim 10, wherein the detectable marker is a fluorescent, enzymatic, heavy metal or radioactive marker. 13. The antibody or antigen binding fragment of claim 10, wherein the chemotherapeutic agent is a toxin. 14. The antibody or antigen binding fragment of claim 13, wherein the toxin is a maytansinoid toxin or an auristatin toxin. 15. The antibody or antigen binding fragment of claim 14, wherein the maytansinoid toxin is DM1; or the auristatin toxin is Monomethyl Auristatin E (MMAE) or Monomethyl Auristatin F (MMAF). 16. The antibody or antigen binding fragment thereof of claim 10, wherein the isolated monoclonal antibody or antigen binding fragment is conjugated to the effector molecule by a cleavable linker. 17. A composition comprising an effective amount of the antibody or antigen binding fragment of claim 1 and a pharmaceutically acceptable carrier. 18. An isolated nucleic acid molecule encoding the antibody or antigen binding fragment of claim 1. 19. A vector comprising the nucleic acid molecule of claim 18. 20. A host cell, comprising the nucleic acid molecule of claim 18. 21. A method of treating a subject with a TEM8-expressing tumor, comprising: administering to the subject a therapeutically effective amount of the antibody or antigen binding fragment of claim 1 under conditions sufficient to form an immune complex, wherein formation of the immune complex treats the tumor in the subject. 22. The method of claim 21, further comprising selecting the subject with the tumor. 23. The method of claim 22, wherein selecting the subject comprises detecting an endothelial cell that expresses TEM8 in the subject. 24. The method of claim 21, further comprising administering to the subject a therapeutically effective amount of an anti-angiogenic agent or a chemotherapeutic agent. 25. The method of claim 24, wherein the anti-angiogenic agent comprises bevacizumab. 26. The method of claim 21, wherein the tumor is breast cancer, colorectal cancer, lung cancer or skin cancer. 27. The method of claim 21, wherein treating the tumor comprises a reduction in tumor burden. 28. The method of claim 21, wherein the isolated monoclonal antibody or antigen binding fragment is conjugated to a chemotherapeutic agent. 29. The method of claim 28, wherein the chemotherapeutic agent is a maytansinoid toxin or an auristatin toxin. 30. A method of detecting an endothelial cell expressing TEM8 in a subject, comprising: contacting an endothelial cell from the subject with an effective amount of the antibody or antigen binding fragment of claim 1 under conditions sufficient to form an immune complex; and detecting the immune complex on the endothelial cell from the subject, wherein the presence of the immune complex on the endothelial cell from the subject detects the endothelial cell expressing TEM8 in the subject. 31. The method of claim 30, wherein the contacting is in vivo. 32. The method of claim 30, wherein the contacting is in vitro. 33. The method of claim 30, wherein detecting the presence of an endothelial cell expressing TEM8 in the subject detects pathological angiogenesis in the subject. 34. The method of claim 30, wherein the endothelial cell is in a biological sample from the subject. 35. A method of decreasing the binding of Anthrax protective antigen to a cell, comprising: contacting the cell with an effective amount of the antibody or antigen binding fragment of claim 1 under conditions sufficient to form an immune complex, wherein formation of the immune complex decreases the binding of Anthrax protective antigen to the cell. 36. The method of claim 35, wherein contacting the cell with an effective amount of the monoclonal antibody or antigen binding fragment comprises administering a therapeutically effective amount of the monoclonal antibody or antigen binding fragment to a subject. 37. A kit for detecting pathological angiogenesis in a subject, treating a tumor in a subject, or decreasing the binding of Anthrax protective antigen to a cell, comprising a container comprising the antibody or antigen binding fragment of claim 1 and instructions for using the kit.

Details for Patent 9,181,340

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	AVASTIN	bevacizumab	Injection	125085	02/26/2004		2031-06-14