COMBINATION OF VACCINATION AND INHIBITION OF THE PD-1 PATHWAY

• US 20160130345A1
• Filed: 02/21/2014
• Published: 05/12/2016
• Est. Priority Date: 02/22/2013
• Status: Active Grant

• Current Assignee: CureVAC SE (f/k/a CureVac AG)
• Original Assignee: CureVac AG (CureVAC SE (f/k/a CureVac AG))
• Inventors: KALLEN, Karl-Josef, FOTIN-MLECZEK, Mariola, PROBST, Jochen
• Granted Patent: US 9,974,845 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/53 DNA (RNA) vaccination
• CPC Class Codes: A61K 2039/55516 Proteins; Peptides
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 39/0005 Vertebrate antigens from snakes A61K39/38
• CPC Class Codes: A61K 39/0011 Cancer antigens
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 39/39558 against tumor tissues, cells, antigens
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 33/00 Antiparasitic agents
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily
• CPC Class Codes: C07K 16/2818 against CD28 or CD152
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention relates to a vaccine/inhibitor combination comprising an RNA vaccine comprising at least one RNA comprising at least one open reading frame (ORF) coding for at least one antigen and a composition comprising at least one PD-1 pathway inhibitor, preferably directed against PD-1 receptor or its ligands PD-L1 and PD-L2. The present invention furthermore relates to a pharmaceutical composition and a kit of parts comprising the components of such a vaccine/inhibitor combination. Additionally the present invention relates to medical use of such a vaccine/inhibitor combination, the pharmaceutical composition and the kit of parts comprising such a vaccine/inhibitor combination, particularly for the prevention or treatment of tumor or cancer diseases or infectious diseases. Furthermore, the present invention relates to the use of an RNA vaccine in therapy in combination with a PD-1 pathway inhibitor and to the use of a PD-1 pathway inhibitor in therapy in combination with an RNA vaccine.

Claims

1-29. -29. (canceled)

30. A method of treating a subject comprising administering to the subject an effective amount of:

(i) an immunogenic composition comprising at least one RNA encoding at least one antigen; and

(ii) a PD-1 pathway inhibitor.

31. The method of claim 30, wherein the PD-1 pathway inhibitor is administered after said immunogenic composition.

32. The method of claim 30, wherein the PD-1 pathway inhibitor comprises an inhibitor directed against PD-1.

33. The method of claim 30, wherein the PD-1 pathway inhibitor comprises an inhibitor directed against PD-L1 or PD-L2.

34. The method of claim 30, wherein the PD-1 pathway inhibitor comprises an antibody, a nucleic acid encoding an antibody or an siRNA that inhibits PD-1 signalling.

35. The method of claim 34, wherein the PD-1 pathway inhibitor is an antibody, or a nucleic-acid encoded antibody, directed against PD-1 or PD-1 ligand.

36. The method of claim 35, wherein the antibody is directed against PD-1 and is selected from the group consisting of Nivolumab (BMS-936558/MDX1106), CT-011 and MK-3475 (SCH 900475).

37. The method of claim 35, wherein the antibody is directed against PD-L1 and is selected from the group consisting of MDX-1105/BMS-936559, MPDL3280A/RG7446, and MEDI4736.

38. The method of claim 30, wherein the PD-1 pathway inhibitor comprises an extracellular domain of PD-1, PD-L1 or PD-L2, or nucleic acid encoding said extracellular domain, that inhibits PD-1 signalling.

39. The method of claim 30, wherein the at least one RNA encodes an infectious disease antigen.

40. The method of claim 30, wherein the at least one RNA encodes a cancer or tumor cell antigen.

41. The method of claim 30, wherein the at least one RNA is an mRNA.

42. The method of claim 30, wherein the RNA is a codon optimized RNA.

43. The method of claim 30, wherein the at least one RNA comprises an increased G/C content relative to a wild type RNA encoding the antigen.

44. The method of claim 30, wherein the at least one RNA is complexed with a carrier.

45. The method of claim 44, wherein the carrier is a cationic, polycationic or polymeric carrier.

46. The method of claim 45, wherein the carrier comprises protamine.

47. The method of claim 30, wherein the subject has a cancer or tumor disease.

48. A kit of parts comprising:

(i) an immunogenic composition comprising at least one RNA encoding at least one antigen; and

(ii) a composition comprising a PD-1 pathway inhibitor.

49. A pharmaceutical composition comprising an effective amount of:

(i) at least one RNA encoding at least one antigen and (ii) a PD-1 pathway inhibitor.