Anti-ceramide antibodies

• US 10,450,385 B2
• Filed: 08/07/2015
• Issued: 10/22/2019
• Est. Priority Date: 08/07/2014
• Status: Active Grant

• Current Assignee: Ceramide Therapeutics, Memorial Sloan-Kettering Cancer Center
• Original Assignee: Memorial Sloan-Kettering Cancer Center
• Inventors: Rotolo, Jimmy, Kolesnick, Richard
• Primary Examiner(s): Wen, Sharon X
• Application Number:
  US15/502,162
• Publication Number:
  US 20170335014A1
• Time in Patent Office: 1,537 Days
• Field of Search: None
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 39/00 General protective or antinoxious agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/28 against receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: C07K 16/44 against material not provided for elsewhere , e.g. haptens, metals, DNA, RNA, amino acids
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/622 Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding

Abstract

Monoclonal antibodies directed to ceramide that inhibit apoptosis are disclosed. Humanized and scFv versions of the antibodies are also disclosed. Methods for prevention or treatment of apoptosis in a subject by administration of the anti-ceramide antibodies are disclosed.

Claims

1. An anti-ceramide antibody or antigen-binding fragment thereof comprising a variable heavy chain (VH) and a variable light chain (VL), wherein

the VH comprises a heavy chain variable region CDR1 comprising the sequence GYTFTDHTIH (SEQ ID NO:

1), a heavy chain variable region CDR2 comprising the sequence YNYPRDGSTKYNEKFKG (SEQ ID NO;

     2), and a heavy chain variable region CDR3 comprising the sequence GFITTVVPSAY (SEQ ID NO;

     3), and

the VL comprises a light chain variable region CDR1 comprising the sequence RASKSISKYLA (SEQ ID NO;

     4), a light chain variable region CDR2 comprising the sequence SGSTLQS (SEQ ID NO;

     5), and a light chain variable region CDR3 comprising the sequence QQHNEYPWT (SEQ ID NO;

     6).

3. The anti-ceramide antibody or antigen-binding fragment of claim 1, wherein the antibody is selected from the group consisting of a monoclonal antibody, a chimeric antibody, a humanized antibody, a human antibody and a scFv.

4. The anti-ceramide antibody of claim 3, wherein the antibody is a scFv.

2. An anti-ceramide antibody or antigen-binding fragment thereof comprising

a heavy chain variable region sequence of QVQLQQSDAELVKPGASVKISCKVSGYTFTDHTIHWMKQRPEQGLEWIGYNYPRDGST KYNEKFKGKATLTADKSSSTAYMQLNSLTSEDSAVYFCAKGFITTVVPSAYWGQGTLV TVSA (SEQ ID NO:

48); and

a light chain variable region sequence of DVQITQSPSYLAASPGETITINCRASKSISKYLAWYQEKPGKTNKLLIYSGSTLQSGIPSRF SGSGSGTDFTLTISSLEPEDFAMYYCQQHNEYPWTFGGGTKLEIK (SEQ ID NO;

     8).