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Summary for Patent: 9,402,916
|Abstract:||The invention provides an agent for preventing or treating a condition characterized by the presence of unwanted cells, the agent comprising: (i) a targeting moiety that is capable of targeting to the unwanted cells; and (ii) a T cell antigen, wherein the T cell antigen can be released from the targeting moiety by selective cleavage of a cleavage site in the agent in the vicinity of the unwanted cells.|
|Inventor(s):||Cobbold; Mark (Birmingham, GB), Millar; David (Birmingham, GB)|
|Assignee:||THE UNIVERSITY OF BIRMINGHAM (Birmingham, GB)|
|Patent Claims:||1. A method of retargeting T cells to cancer cells, the method comprising administering an agent for treating cancer to a human subject in need thereof, wherein the
agent comprises: i) a targeting moiety that is capable of targeting to the cancer cells, wherein the targeting moiety is an antibody or antigen binding fragment thereof that binds a tumor antigen; and ii) a viral T cell epitope that elicits an existing
immune response in the subject and binds to a HLA molecule on the surface of the cancer cell of the human subject and has a HLA matched to the subject, and iii) a peptide linker comprising a peptide cleavage site cleavable by a tumor associated protease
and wherein the linker can be selectively cleaved by the tumor associated protease to release the T cell epitope in the vicinity of, and outside of, the cancer cell.
2. The method according to claim 1, further comprising determining any one of (i) HLA alleles of the subject, (ii) cytotoxic T cell response of the subject to a T cell epitope (iii) expression profile of the cancer cell in the subject.
3. The method according to claim 1, further comprising administering a therapeutic agent suitable for treating cancer.
4. The method of claim 1, wherein the antibody is Rituximab or Cetuximab.
5. The method of claim 1, wherein the T cell epitope is a peptide from Varicella Zoster virus, Herpes simplex virus, cytomegalovirus, Epstein Barr virus, adenovirus, rhinovirus, or influenza virus.
6. The method of claim 1, wherein the T cell epitope is a cytomegalovirus peptide.
7. The method of claim 1, wherein the T cell epitope is NLVPMVATV (SEQ ID NO: 21), TPRVTGGGAM (SEQ ID NO: 31), DYSNTHSTRYV (SEQ ID NO: 55), YVLEETSVM (SEQ ID NO: 3), or VLEETSVML (SEQ ID NO: 4).
8. The method of claim 1, wherein the T cell epitope is NLVPMVATV (SEQ ID NO: 21).
9. The method of claim 1, wherein the antibody or antigen binding fragment thereof is specific for any of Her2/Neu; CD22; EpCAM (CD326); EGFR; PMSA; CD30; CD20; CD33; membrane IgE; IgE Receptor (CD23), CD80; CD86; CD2; CA125; Carbonic Anhydrase IX; CD70; CD74; CD56; CD40; CD19; c-met/HGFR; TRAIL-R1; DR5; PD-1; PD1L; IGF-1R; VEGF-R2; Prostate stem cell antigen (PSCA); MUC1; CanAg; Mesothelin; P-cadherin; Myostatin (GDF8); Cripto (TDGF1); ACVRL1/ALK1; MUC5AC; CEACAM; SLC44A4; CD2/CS1; CD137; CXCR4; Neuropilin 1; Glypican; HER3/EGFR; PDGFRa, EphA2, CD22, E-cadherin, FGFR3, and CD138.
10. The method of claim 1, wherein the antibody or antigen binding fragment thereof binds to CD20 or EGFR and the T cell epitope is a cytomegalovirus peptide.
11. The method of claim 10, wherein the T cell epitope is NLVPMVATV (SEQ ID NO: 21).
12. The method of claim 1, wherein the tumor associated protease is a cysteine protease, an aspartyl protease, a serine protease, or a metalloprotease.
13. The method of claim 1, wherein the tumor associated protease is Cathepsin B, Cathepsin L, Cathepsin S, Cathepsin D, Cathepsin E, Cathepsin A, Cathepsin G, Thrombin, Plasmin, Urokinase, Tissue Plasminogen Activator, Metalloproteinase 1 (MMP1), MMP2, MMP3, MMP4, MMP7, MMP8, MMP9, MMP10, MMP11, MMP12, MMP13, MMP14, MMP15, MMP16, MMP17, MMP20, MMP21, MMP23, MMP24, MMP25, MMP26, MMP28, ADAM, ADAMTS, CD10 (CALLA), or prostate specific antigen.
14. The method of claim 1, wherein the tumor associated protease is a metalloprotease or a cathepsin.
15. The method of claim 1, wherein the tumor associated protease is MMP2, ADAM28, or Cathepsin B.
16. The method of claim 11, wherein the tumor associated protease is ADAM28.
17. The method of claim 1, wherein the T cell epitope is an MHC Class I restricted antigen, an MHC Class II restricted antigen, or an antigen that is capable of binding to a group I CD1 molecule.
Summary for Patent: Start Trial
|Foriegn Application Priority Data|
|Foreign Country||Foreign Patent Number||Foreign Patent Date|
|United Kingdom||1104514.3||Mar 17, 2011|
|United Kingdom||1203434.4||Feb 28, 2012|
|PCT Filed||March 15, 2012||PCT Application Number:||PCT/GB2012/050577|
|PCT Publication Date:||September 20, 2012||PCT Publication Number:||WO2012/123755|
|Applicant||Tradename||Biologic Ingredient||Dosage Form||BLA||Number||Approval Date||Patent No.||Assignee||Estimated Patent Expiration||Status||Orphan||Source|
|Microbix Biosystems||KINLYTIC||urokinase||INJECTABLE;INJECTION||021846||001||1978-01-16||Start Trial||THE UNIVERSITY OF BIRMINGHAM (Birmingham, GB)||2031-03-17||DISCN||search|
|Microbix Biosystems||KINLYTIC||urokinase||INJECTABLE;INJECTION||021846||002||1978-01-16||Start Trial||THE UNIVERSITY OF BIRMINGHAM (Birmingham, GB)||2031-03-17||DISCN||search|
|Microbix Biosystems||KINLYTIC||urokinase||INJECTABLE;INJECTION||021846||003||1978-01-16||Start Trial||THE UNIVERSITY OF BIRMINGHAM (Birmingham, GB)||2031-03-17||DISCN||search|
|Genentech||RITUXAN||rituximab||SOLUTION;INTRAVENOUS||103705||001||1997-11-26||Start Trial||THE UNIVERSITY OF BIRMINGHAM (Birmingham, GB)||2031-03-17||RX||search|
|Genentech||RITUXAN||rituximab||SOLUTION;INTRAVENOUS||103705||002||1997-11-26||Start Trial||THE UNIVERSITY OF BIRMINGHAM (Birmingham, GB)||2031-03-17||RX||search|
|>Applicant||>Tradename||>Biologic Ingredient||>Dosage Form||>BLA||>Number||>Approval Date||>Patent No.||>Assignee||>Estimated Patent Expiration||>Status||>Orphan||>Source|
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