Claims for Patent: 10,294,299

Summary for Patent: 10,294,299

Title:	Immunological reagents
Abstract:	This disclosure relates to binding agents with specificity for programmed cell death 1 (PD-1) and to methods for using the same to treat, prevent and/or ameliorate an infectious disease (e.g., human immunodeficiency virus (HIV)), cancer and/or autoimmunity. In addition, this disclosure identifies a novel binding patch (\"P2\") on PD-1 that is linked with a previously unidentified functional activity of PD-1 that is distinct from the interaction site involved with either the PD-L1 or PD-L2 ligands. Furthermore, we demonstrate that antibodies that interact with this region of PD-1 are able to act as antagonists of PD-1 and that this antagonism is further enhanced with the addition of antibodies that act through the blockade of the PD-1/PD-L1/L2 interaction.
Inventor(s):	Pantaleo; Giuseppe (Pully, CH), Fenwick; Craig (Lausanne, CH)
Assignee:	MabQuest SA (Pully, CH)
Application Number:	15/513,395
Patent Claims:	1. A humanized antibody or fragment thereof that binds human PD-1 and comprises a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO: 176 and a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO: 190. 2. A composition comprising the humanized antibody or fragment thereof of claim 1 and at least one pharmaceutically acceptable carrier. 3. A method of inducing internalization of PD-1 from the surface of a T cell by contacting the T cell with the composition of claim 2. 4. The method of claim 3, wherein the T cell is a human T cell infected with human immunodeficiency virus (HIV). 5. A method of relieving functional exhaustion and increasing proliferation of antigen-specific CD8 T cells by contacting the CD8 T cells with the composition of claim 2. 6. The method of claim 5, wherein the T cells are specific for human immunodeficiency virus (HIV). 7. The method of claim 3 or 5, wherein the method further comprises contacting the T cells with the anti-PD-1 antibody pembrolizumab. 8. A method of treating cancer in a human patient, the method comprising administering to the patient with the cancer an effective amount of the composition of claim 2. 9. The method of claim 8, wherein the method further comprises administering pembrolizumab to the patient. 10. The fragment of claim 1, wherein the fragment is an F.sub.ab, F.sub.ab2, Fab', single chain antibody, or F.sub.v fragment. 11. A composition comprising the fragment of claim 10 and at least one pharmaceutically acceptable carrier. 12. A composition comprising the humanized antibody or fragment thereof of claim 1 and the anti-PD-1 antibody pembrolizumab. 13. A binding agent that comprises the humanized antibody or fragment thereof of claim 1 and a second binding specificity against a different antigen. 14. A composition comprising the binding agent of claim 13 and a pharmaceutically acceptable carrier. 15. A derivative of the humanized antibody or fragment thereof of claim 1, wherein the derivative comprises the humanized antibody or fragment thereof of claim 1 and a detectable label or an effector moiety fixably attached thereto. 16. A composition comprising the derivative of claim 15 and a pharmaceutically acceptable carrier. 17. An isolated polynucleotide encoding a humanized antibody or fragment thereof that binds human PD-1 and comprises a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO: 176 and a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO: 190. 18. An isolated polynucleotide comprising the nucleic acid sequence set forth in SEQ ID NO: 229 or SEQ ID NO: 243. 19. An expression vector comprising one or more polynucleotide of claim 17 or 18. 20. A host cell comprising the expression vector of claim 19. 21. A host cell comprising one or more polynucleotide of claim 17 or 18. 22. A humanized antibody or fragment thereof that binds human PD-1 and comprises a combination of a heavy chain variable region (VH) and a light chain variable region (VL), wherein the humanized antibody comprises: (a) a VH comprising an amino acid sequence as set forth in one of SEQ ID NOS: 147-150 and a VL comprising an amino acid sequence set forth in one of SEQ ID NOS: 159-163; or (b) a VH comprising an amino acid sequence as set forth in one of SEQ ID NOS: 172-177 and a VL comprising an amino acid sequence as set forth in one of SEQ ID NOS: 186-190. 23. A composition comprising the humanized antibody or fragment thereof of claim 22 and a pharmaceutically acceptable carrier. 24. A composition comprising the humanized antibody or fragment thereof of claim 22 and the anti-PD-1 antibody pembrolizumab. 25. A method of treating cancer in a human patient, the method comprising administering to the patient with the cancer an effective amount of the composition of claim 22. 26. The method of claim 25, wherein the method further comprises administering pembrolizumab to the patient. 27. An isolated polynucleotide encoding a humanized antibody or fragment that binds human PD-1 and comprises a combination of a heavy chain variable region (VH) and a light chain variable region (VL), wherein the humanized antibody comprises: (a) a VH encoded by a nucleic acid sequence as set forth in one of SEQ ID NOS: 200-203 and a VL encoded by a nucleic acid sequence as set forth in one of SEQ ID NOS: 212-216; or (b) a VH encoded by a nucleic acid sequence as set forth in one of SEQ ID NOS: 225-230 and a VL encoded by a nucleic acid sequence as set forth in one of SEQ ID NOS: 239-243. 28. A vector comprising the polynucleotide of claim 27. 29. A host cell comprising the vector of claim 28.

Details for Patent 10,294,299

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Corp.	KEYTRUDA	pembrolizumab	For Injection	125514	09/04/2014		2036-01-22
Merck Sharp & Dohme Corp.	KEYTRUDA	pembrolizumab	Injection	125514	01/15/2015		2036-01-22