Methods and compositions for the treatment of hcmv

Patent metadata

Field	Value
Publication number	US-2016289303-A1
Application number	US-201415036092-A
Country	US
Kind code	A1
Filing date	Nov 14, 2014
Priority date	Nov 15, 2013
Publication date	Oct 6, 2016
Grant date	—

Abstract

Provided herein are compositions and methods for the treatment of HCMV infection in a subject.

First claim

1 . A method of treating HCMV in a subject comprising administering to the subject an agent that specifically binds to a protein encoded by a gene selected from the genes listed in Table 1.

2 . The method of claim 1 , wherein the protein is encoded by a gene selected from the genes listed in Table 2.

3 . The method of claim 1 , wherein the agent is an antibody.

4 . The method of claim 3 , wherein the antibody is monoclonal.

5 . The method of claim 3 , wherein the antibody is chimeric, humanized or fully human.

6 . The method of claim 3 , wherein the antibody is selected from the group consisting of:
a full length immunoglobulin molecule; an scFv; a Fab fragment; an Fab′ fragment; an F(ab′)2; an Fv; a NANOBODY®; and a disulfide linked Fv.

7 . The method of claim 3 , wherein the antibody binds to the protein with a dissociation constant of no greater than about 10 −7 M.

8 . The method of claim 3 , wherein the antibody binds to an extracellular epitope of the protein.

9 . The method of claim 8 , wherein the epitope is selected from the epitopes listed in Table 5.

10 . The method of claim 3 , wherein the antibody is linked to a cytotoxic agent.

11 . The method of claim 10 , wherein the cytotoxic agent is selected from the group consisting of MMAE, DM-1, maytansinoids, doxorubicin derivatives, auristatins, calcheamicin, CC-1065, duocarmycins and anthracyclines.

12 . The method of claim 3 , wherein the antibody is linked to an antiviral agent.

13 . The method of claim 12 , wherein the antiviral agent is ganciclovir, valganciclovir, foscarnet, cidofovir, acyclovir, formivirsen, maribavir, BAY 38-4766 or GW275175X.

14 . An antibody that specifically binds to an extracellular epitope of a protein encoded by a gene selected from the genes listed in Table 1.

15 . The antibody of claim 14 , wherein the protein is encoded by a gene selected from the genes listed in Table 2.

16 . The antibody of claim 14 , wherein the epitope is selected from the epitopes listed in Table 5.

17 . The antibody of claim 14 , wherein the antibody is monoclonal.

18 . The antibody of claim 14 , wherein the antibody is chimeric, humanized or fully human.

19 . The antibody of claim 14 , wherein the antibody is selected from the group consisting of:
a full length immunoglobulin molecule; an scFv; a Fab fragment; an Fab′ fragment; an F(ab′)2; an Fv; a NANOBODY®; and a disulfide linked Fv.

20 . The antibody of claim 14 , wherein the antibody binds to the target protein with a dissociation constant of no greater than about 10 −7 M.

21 . The antibody of claim 14 , wherein the antibody is linked to a cytotoxic agent.

22 . The antibody of claim 21 , wherein the cytotoxic agent is selected from the group consisting of MMAE, DM-1, maytansinoids, doxorubicin derivatives, auristatins, calcheamicin, CC-1065, duocarmycins and anthracyclines.

23 . The antibody of 14 , wherein the antibody is linked to an antiviral agent.

24 . The antibody of claim 23 , wherein the antiviral agent is ganciclovir, valganciclovir, foscarnet, cidofovir, acyclovir, formivirsen, maribavir, BAY 38-4766 or GW275175X.

25 . A method of treating HCMV in a subject comprising administering to the subject an agent that specifically binds to a protein encoded by a group consisting of the genes listed in Table 3.

26 . The method of claim 25 , wherein the protein is encoded by a gene selected from the group consisting of CHST11, KCNK1, SPINT1, CDH1, CEACAM1, EPCAM, TNFRSF1B, ERBB3, CNTFR, PCDH1, BST2, SDK2, RALGPS2, SLCO4A1, MEGF10, SEMA4D, PCDH1, SPINT1 and TTC17.

27 . The method of claim 25 , wherein the agent is an antibody.

28 . The method of claim 27 , wherein the antibody is monoclonal.

29 . The method of claim 27 , wherein the antibody is chimeric, humanized or fully human.

30 . The method of claim 27 , wherein the antibody is selected from the group consisting of:
a full length immunoglobulin molecule; an scFv; a Fab fragment; an Fab′ fragment; an F(ab′)2; an Fv; a NANOBODY®; and a disulfide linked Fv.

31 . The method of claim 27 , wherein the antibody binds to the protein with a dissociation constant of no greater than about 10 −7 M.

32 . The method of claim 27 , wherein the antibody binds to an extracellular epitope of the protein.

33 . The method of claim 27 , wherein the antibody is linked to a cytotoxic agent.

34 . The method of claim 33 , wherein the cytotoxic agent is selected from the group consisting of MMAE, DM-1, maytansinoids, doxorubicin derivatives, auristatins, calcheamicin, CC-1065, duocarmycins and anthracyclines.

35 . The method of claim 27 , wherein the antibody is linked to an antiviral agent.

36 . The method of claim 35 , wherein the antiviral agent is ganciclovir, valganciclovir, foscarnet, cidofovir, acyclovir, formivirsen, maribavir, BAY 38-4766 or GW275175X.

37 . An antibody that specifically binds to an extracellular epitope of a protein encoded by a group consisting of the genes listed in Table 3.

38 . The antibody of claim 37 , wherein the protein is encoded by a gene selected from the group consisting of CHST11, KCNK1, SPINT1, CDH1, CEACAM1, EPCAM, TNFRSF1B, ERBB3, CNTFR, PCDH1, BST2, SDK2, RALGPS2, SLCO4A1, MEGF10, SEMA4D, PCDH1, SPINT1 and TTC17.

39 . The antibody of claim 37 , wherein the antibody is monoclonal.

40 . The antibody of claim 39 , wherein the antibody is chimeric, humanized or fully human.

41 . The antibody of claim 39 , wherein the antibody is selected from the group consisting of:
a full length immunoglobulin molecule; an scFv; a Fab fragment; an Fab′ fragment; an F(ab′)2; an Fv; a NANOBODY®; and a disulfide linked Fv.

42 . The antibody of claim 39 , wherein the antibody binds to the target protein with a dissociation constant of no greater than about 10 −7 M.

43 . The antibody of claim 39 , wherein the antibody is linked to a cytotoxic agent.

44 . The antibody of claim 43 , wherein the cytotoxic agent is selected from the group consisting of MMAE, DM-1, maytansinoids, doxorubicin derivatives, auristatins, calcheamicin, CC-1065, duocarmycins and anthracyclines.

45 . The antibody of claim 39 , wherein the antibody is linked to an antiviral agent.

46 . The antibody of claim 45 , wherein the antiviral agent is ganciclovir, valganciclovir, foscarnet, cidofovir, acyclovir, formivirsen, maribavir, BAY 38-4766 or GW275175X.

47 . A method of treating HCMV in a subject comprising administering to the subject a cytotoxic agent to which a protein encoded by ABCC3, SLC38A4 or SLC2A10 provides cellular resistance.

48 . The method of claim 47 , wherein the protein is encoded by ABCC3.

49 . The method of claim 48 , wherein the cytotoxic agent is Etoposide.

50 . The method of claim 47 , wherein the protein is encoded by SLC38A4.

51 . The method of claim 47 , wherein the protein is encoded by SLC2A10.

Assignees

• Harvard College
• Cambridge Univ
• Univ Cardiff

Inventors

• Weekes Michael P
• Gygi Steven P
• Lehner Paul J
• Wilkinson Gavin W
• Tomasec Peter
• Stanton Richard J

Classifications

• A61K31/7048

  having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin {, digitoxin or digoxin} · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• C07K2317/34

  Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues · CPC title

• C07K2317/732

  Antibody-dependent cellular cytotoxicity [ADCC] · CPC title

• A61K47/6839

  the antibody targeting material from viruses · CPC title