IP Library › Patent Application 15562602
Patent Application
App. No. 15/562,602

INHIBITORS OF NEUROLIGIN 4 - NEUREXIN 1-BETA PROTEIN-PROTEIN INTERACTION FOR TREATMENT OF LIVER DISORDERS

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Quick Facts
Patent No.
US None
App. No.
15/562,602
Abstract

Provided is a method for treating, attenuating and/or preventing progression of a liver disorder in a subject, the method including administering a therapeutically effective amount of an agent capable of interfering with, inhibiting and/or preventing neuroligin 4 (NLGn4)-Neurexin 1-beta (Nrx1b) protein-protein interaction. Also provided are compositions including the agent.

Claims (19)

1 .- 21 . (canceled)

22 . A composition comprising a therapeutically effective amount of an agent capable of interfering with, inhibiting and/or preventing neuroligin 4 (NLGn4)-Neurexin 1β (Nrx1b) protein-protein interaction and a pharmaceutically acceptable carrier wherein the therapeutic agent comprises an anti-NLGn4 antibody, or a fragment, derivative or analog thereof, comprising at least the antigen binding portion thereof.

23 . The composition of claim 22 , wherein the anti-NLGn4 antibody is capable of binding specifically to amino acids 359-364 of the human NLGN4 protein.

24 . The composition of claim 22 , wherein the anti-NLGn4 antibody is capable of binding to an epitope within a sequence selected from the group of: residues 261-270 of the human NLGn4, as set forth in SEQ ID NO: 3 (SLLTLSHYSE); residues 265-275, as set forth in SEQ ID NO: 5 (LSHYSEGLFQK), of the human NLGn4; and residues 461-470 of the human NLGn4, as set forth in SEQ ID NO: 4 (AQYGSPTYFY).

25 . A method of treating, attenuating and/or preventing progression of a liver disorder, comprising administering a therapeutically effective amount of an agent capable of interfering with, inhibiting and/or preventing neuroligin 4 (NLGn4)-Neurexin 1β (Nrx1b) protein-protein interaction and a pharmaceutically acceptable carrier, thereby treating, attenuating and/or preventing progression of a liver disorder.

26 . The method of claim 25 , wherein the agent comprises recombinant soluble NLGn4 (rsNLGn4); wherein the rsNLGn4 comprises the extracellular domain of NLGn4 or a fragment, derivative or analog thereof.

27 . The method of claim 26 , wherein the extracellular domain of NLGn4 consists of SEQ ID NO: 7; or wherein the rsNLGn4 consists of SEQ ID NO: 7, or a fragment, derivative or analog thereof; or wherein the rsNLGn4 competes with endogenous NLGn4 for binding to Nrx1b; or wherein the rsNLGn4 is devoid of the intracellular domain and/or the transmembrane domain of NLGn4.

28 . The method of claim 25 , wherein the agent comprises recombinant soluble Nrx1b (rsNrx1b); wherein the rsNrx1b comprises the extracellular domain of Nrx1b or a fragment, derivative or analog thereof capable of binding the NLGn4.

29 . The method of claim 28 , wherein the extracellular domain of Nrx1b consists of SEQ ID NO: 10; wherein the rsNrx1b consists of SEQ ID NO: 10, or a fragment, derivative or analog thereof; wherein the rsNrx1b competes with endogenous Nrx1b for binding to NLGn4; or wherein the rsNrx1b is devoid of the intracellular domain and/or the transmembrane domain of Nrx1b.

30 . The method of claim 25 , wherein NLGn4 is encoded by the sequence set forth in SEQ ID NO: 1.

31 . The method of claim 25 , wherein Nrx1b is encoded by the sequence set forth in SEQ ID NO: 6.

32 . The method of claim 25 , the agent comprises a fusion protein comprising the Fc portion of an immunoglobulin molecule and SEQ ID NO: 7 or a fragment thereof.

33 . The method of claim 25 , wherein the agent comprises a fusion protein comprising the Fc portion of an immunoglobulin molecule and SEQ ID NO: 10 or a fragment thereof.

34 . The method of claim 25 , wherein the therapeutic agent comprises an anti-NLGn4 antibody, or a fragment, derivative or analog thereof, comprising at least the antigen-binding portion thereof; wherein the anti-NLGn4 antibody is capable of binding specifically to an interaction domain of human NLGn4.

35 . The method of claim 34 , wherein the anti-NLGn4 antibody is capable of binding specifically to amino acids 359-364 of the human NLGN4 protein.

36 . The method of claim 34 , wherein the anti-NLGn4 antibody is capable of binding to an epitope within a sequence selected from the group of: residues 261-270 of the human NLGn4, as set forth in SEQ ID NO: 3 (SLLTLSHYSE); residues 265-275, as set forth in SEQ ID NO: 5 (LSHYSEGLFQK), of the human NLGn4; and residues 461-470 of the human NLGn4, as set forth in SEQ ID NO: 4 (AQYGSPTYFY).

37 . The method of claim 25 , wherein the liver disorder is selected from the group consisting of: non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), cirrhosis, hepatitis, liver adenoma, insulin hypersensitivity, liver cancer and any combination thereof.

38 . The method of claim 37 , wherein the liver disorder is NAFLD.

39 . The composition of claim 37 , wherein the liver disorder is hepatocellular carcinoma.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 28, 2017
From: SAFADI, RIFAAT
To: HADASIT MEDICAL RESEARCH SERVICES AND DEVELOPMENT LTD.
Reel/Frame 043726/0575 →