Claims for Patent: 9,868,789

Summary for Patent: 9,868,789

Title:	Synergistic combinations of OX40L antibodies for the treatment of GvHD
Abstract:	The present invention relates to anti-human OX40L antibodies, new medical uses and methods.
Inventor(s):	Bland-Ward; Philip (Cambridge, GB), Kosmac; Miha (Cambridge, GB), Holmes; Steve (Cambridge, GB), Kirby; Ian (Cambridge, GB), Campbell; Jamie (Cambridge, GB)
Assignee:	Kymab Limited (GB)
Application Number:	15/604,495
Patent Claims:	1. A method of treating or preventing transplant rejection in a primate subject in need thereof, comprising: administering intravenously to the subject: a) at least one anti-OX40L antibody or fragment thereof that antagonizes specific binding of OX40 to OX40L; and b) at least one CTLA4-Fc; wherein the at least one anti-OX40L antibody or fragment thereof is intravenously administered at a dose of about 5 mg/kg to about 20 mg/kg on the day of transplant and at a dose of about 1 mg/kg to about 10 mg/kg at least once a week following the day of the transplant; and wherein the at least one CTLA4-Fc is intravenously administered at a dose of about 5 mg/kg to about 20 mg/kg on the day of transplant and at a dose of about 5 mg/kg to about 20 mg/kg at least bi-weekly following the day of the transplant. 2. The method of claim 1, wherein the at least one CTLA4-Fc is abatacept. 3. The method of claim 1, wherein the at least one anti-OX40L antibody or fragment thereof is also administered at least once before a transplant. 4. The method of claim 1, wherein the at least one CTLA4-Fc is also administered at least once before a transplant. 5. The method of claim 1, wherein the at least one anti-OX40L antibody or fragment thereof and the at least one CTLA4-Fc are also administered at least once before transplant. 6. The method of claim 1, wherein the at least one anti-OX40L antibody or fragment thereof is humanized or human. 7. The method of claim 1, wherein the at least one anti-OX40L antibody or fragment thereof is selected from the group consisting of multi-specific antibodies, bi-specific antibodies, single chain Fv antibodies (scFv), camelized antibodies, Fab fragments, F(ab') fragments, disulfide-linked Fvs (sdFv), and epitope-binding fragments thereof. 8. The method of claim 1, wherein the at least one anti-OX40L antibody or fragment thereof comprises a HCDR3 of from 16 to 27 amino acids and derived from the recombination of a human VH gene segment, a human D gene segment and a human JH gene segment, wherein the human JH gene segment is IGHJ6 or IGHJ6*02. 9. The method of claim 1, wherein the at least one anti-OX40L antibody or fragment thereof comprises a CDR selected from: a. the HCDR3 sequence of Seq ID No:40 or Seq ID No:46; b. the HCDR3 sequence of Seq ID No:8 or SEQ ID No:14; c. the HCDR3 sequence of Seq ID No:72 or Seq ID No:78; d. the HCDR3 sequence of Seq ID No:100 or Seq ID No:106; e. the HCDR3 sequence of an antibody having the variable region amino acid sequence of Seq ID No: 215, 217, 219, 221, 223, 225, 227, 229 or 230; and f. the HCDR3 sequence of an antibody having the variable region amino acid sequence of Seq ID No: 232 or 234. 10. The method of claim 1, wherein the at least one anti-OX40L antibody or fragment thereof comprises: a. the CDRs of Seq ID No:40 or Seq ID No:46 for CDRH3, SEQ ID No:38 or SEQ ID No:44 for CDRH2, SEQ ID No:36 or SEQ ID No:42 for CDRHI, SEQ ID No:50 or SEQ ID No:56 for CDRL1, SEQ ID No:52 or SEQ ID No:58 for CDRL2, and SEQ ID No:54 or SEQ ID No:60 for CDRL3; b. the CDRs of Seq ID No:8 or SEQ ID No:14 for CDRH3, SEQ ID No:6 or SEQ ID No:12 for CDRH2, SEQ ID No:4 or SEQ ID No:10 for CDRH1, SEQ ID No:18 or SEQ ID No:24 for CDRL1, SEQ ID No:20 or SEQ ID No:26 for CDRL2, and SEQ ID No:22 or SEQ ID No:28 for CDRL3; c. the CDRs of Seq ID No:72 or Seq ID No:78 for CDRH3, SEQ ID No:70 or SEQ ID No:76 for CDRH2, SEQ ID No:68 or SEQ ID No:74 for CDRH1, SEQ ID No:82 or SEQ ID No:88 for CDRL1, SEQ ID No:84 or SEQ ID No:90 for CDRL2, and SEQ ID No:86 or SEQ ID No:92 for CDRL3; d. the CDRs of Seq ID No:100 or Seq ID No:106 for CDRH3, SEQ ID No:98 or SEQ ID No:104 for CDRH2, SEQ ID No:96 or SEQ ID No: 102 for CDRH1, SEQ ID No:110 or SEQ ID No:116 for CDRL1, SEQ ID No:112 or SEQ ID No:118 for CDRL2, and SEQ ID No:114 or SEQ ID No:120 for CDRL3; e. the heavy chain CDRs and the light chain CDRs of variable region amino acid sequences SEQ ID NO: 215 and SEQ ID NO: 214; SEQ ID NO: 217 and SEQ ID NO: 216; SEQ ID NO: 219 and SEQ ID NO: 218; SEQ ID NO: 221 and SEQ ID NO: 220; SEQ ID NO: 223 and SEQ ID NO: 222; SEQ ID NO: 225 and SEQ ID NO: 224; SEQ ID NO: 225 and SEQ ID NO: 226; SEQ ID NO: 227 and SEQ ID NO: 214; SEQ ID NO: 229 and SEQ ID NO: 228; or SEQ ID NO: 230 and SEQ ID NO: 214; f. the heavy chain CDRs and the light chain CDRs of variable region amino acid sequences SEQ ID NO: 232 and SEQ ID NO: 231; or SEQ ID NO: 234 and SEQ ID NO: 233; g. the VH and/or VL domains of Seq ID No:34 for VH and/or Seq ID No:48 for VL; h. the VH and/or VL domains of Seq ID No:2 for VH and/or Seq ID No:16 for VL; i. the VH and/or VL domains of Seq ID No:66 for VH and/or Seq ID No:80 for VL; j. the VH and/or VL domains of Seq ID No:94 for VH and/or Seq ID No:108 for VL; k. the VH domain and the VL domain of amino acid sequences SEQ ID NO: 215 and SEQ ID NO: 214; SEQ ID NO: 217 and SEQ ID NO: 216; SEQ ID NO: 219 and SEQ ID NO: 218; SEQ ID NO: 221 and SEQ ID NO: 220; SEQ ID NO: 223 and SEQ ID NO: 222; SEQ ID NO: 225 and SEQ ID NO: 224; SEQ ID NO: 225 and SEQ ID NO: 226; SEQ ID NO: 227 and SEQ ID NO: 214; SEQ ID NO: 229 and SEQ ID NO: 228; or SEQ ID NO: 230 and SEQ ID NO: 214; or I. the VH domain and the VL domain of amino acid sequences SEQ ID NO: 232 and SEQ ID NO: 231; or SEQ ID NO: 234 and SEQ ID NO: 233. 11. The method of claim 1, wherein the at least one anti-OX40L antibody or fragment thereof comprises the VH sequence of SEQ ID No:215 and the VL sequence of SEQ ID No:214. 12. The method of claim 1, wherein the at least one anti-OX40L antibody or fragment thereof is oxelumab. 13. The method of claim 1, wherein the transplant rejection is renal transplant rejection. 14. The method of claim 1, wherein the primate is human. 15. The method of claim 14, wherein the at least one anti-OX40L antibody or fragment thereof is intravenously administered at a dose of about 5 mg/kg to about 10 mg/kg on the day of transplant and at a dose of about 1 mg/kg to about 5 mg/kg at least once a week following the day of the transplant; and wherein the at least one CTLA4-Fc is intravenously administered at a dose of about 5 mg/kg to about 10 mg/kg on the day of transplant and a dose of about 5 mg/kg to about 10 mg/kg at least biweekly following the day of the transplant. 16. The method of claim 1, wherein the primate is rhesus macaque. 17. The method of claim 16, wherein the at least one anti-OX40L antibody or fragment thereof is intravenously administered at a dose of about 20 mg/kg on the day of transplant and at a dose of about 10 mg/kg at least once a week following the day of the transplant; and wherein the at least one CTLA4-Fc is intravenously administered at a dose of about 20 mg/kg on the day of transplant and a dose of about 20 mg/kg at least biweekly following the day of the transplant. 18. The method of claim 1, wherein the at least one CTLA4-Fc is administered for no more than 84 days and/or 9 doses. 19. The method of claim 1, wherein the at least one anti-OX40L antibody or fragment thereof is administered for no more than 42 days and/or 8 doses.

Details for Patent 9,868,789

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Bristol-myers Squibb Company	ORENCIA	abatacept	For Injection	125118	12/23/2005		2035-09-09
Bristol-myers Squibb Company	ORENCIA	abatacept	Injection	125118	07/29/2011		2035-09-09
Bristol-myers Squibb Company	ORENCIA	abatacept	Injection	125118	06/07/2016		2035-09-09